Therapeutic targets for rheumatoid arthritis: Progress and promises

References

• Sharma, P., and K. Pathak. 2012. Are biological targets the final goal for rheumatoid arthritis therapy? Expert Opin. Biol. Ther. 12: 1611–1622
   PubMed Web of Science ®Google Scholar
• Fan, L., Q. Wang, R. Liu, et al. 2012. Citrullinated fibronectin inhibits apoptosis and promotes the secretion of pro-inflammatory cytokines in fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res. Ther. 14: R266
   PubMed Web of Science ®Google Scholar
• Vinay, D. S., and B. S. Kwon. 2012. Targeting TNF superfamily members for therapeutic intervention in rheumatoid arthritis. Cytokine 57: 305–312
   PubMedGoogle Scholar
• Rasheed, Z., and T. M. Haqqi. 2008. Update on targets of biologic therapies for rheumatoid arthritis. Curr. Rheumatol. Rev. 4: 246
   PubMedGoogle Scholar
• Abe, T., and T. Takeuchi. 2001. Rheumatoid arthritis and tumor necrosis factor alpha. Autoimmunity 34: 291–303
   PubMed Web of Science ®Google Scholar
• Choi, S. I., and E. Brahn. 2010. Rheumatoid arthritis therapy: advances from bench to bedside. Autoimmunity 43: 478–492
   PubMed Web of Science ®Google Scholar
• Choy, E. H., A. F. Kavanaugh, and S. A. Jones. 2013. The problem of choice: current biologic agents and future prospects in RA. Nat. Rev. Rheumatol. 9: 154–163
   PubMed Web of Science ®Google Scholar
• Burli, R. W., A. F. Haughan, and A. J. Hodges. Development of small-molecule therapies for autoimmune diseases. Autoimmunity 43: 526–538
   Google Scholar
• Emery, P. 2012. Optimizing outcomes in patients with rheumatoid arthritis and an inadequate response to anti-TNF treatment. Rheumatology (Oxford) 51: v22–30
   PubMed Web of Science ®Google Scholar
• Moots, R. J., and B. Naisbett-Groet. 2012. The efficacy of biologic agents in patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor inhibitors: a systematic review. Rheumatology (Oxford) 51: 2252–2261
   PubMedGoogle Scholar
• Nishimoto, N. 2005. Cytokine signal regulation and autoimmune disorders. Autoimmunity 38: 359–367
   PubMed Web of Science ®Google Scholar
• Chao, C. C., S. J. Chen, I. E. Adamopoulos, et al. 2011. Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis. Autoimmunity 44: 243–252
   PubMed Web of Science ®Google Scholar
• Conde, J., M. Scotece, V. Lopez, et al. 2013. Adipokines: novel players in rheumatic diseases. Discov. Med. 15: 73–83
   PubMed Web of Science ®Google Scholar
• Gomez, R., J. Conde, M. Scotece, et al. 2011. What's new in our understanding of the role of adipokines in rheumatic diseases? Nat. Rev. Rheumatol. 7: 528–536
   PubMed Web of Science ®Google Scholar
• Rouhiainen, A., J. Kuja-Panula, S. Tumova, and H. Rauvala. 2013. RAGE-mediated cell signaling. Methods Mol. Biol. 963: 239–263
   PubMedGoogle Scholar
• Raucci, A., R. Palumbo, and M. E. Bianchi. 2007. HMGB1: a signal of necrosis. Autoimmunity 40: 285–289
   PubMed Web of Science ®Google Scholar
• Mosquera, J. A. 2010. Role of the receptor for advanced glycation end products (RAGE) in inflammation. Invest Clin. 51: 257–268
   PubMedGoogle Scholar
• Radia, A. M., A. M. Yaser, X. Ma, et al. 2013. Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines. Int. J. Mol. Sci. 14: 7959–7978
   PubMed Web of Science ®Google Scholar
• Rasheed, Z., A. N. Anbazhagan, N. Akhtar, et al. 2009. Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes. Arthritis Res. Ther. 11: R71
   PubMed Web of Science ®Google Scholar
• Thalhamer, T., M. A. McGrath, and M. M. Harnett. 2008. MAPKs and their relevance to arthritis and inflammation. Rheumatology (Oxford) 47: 409–414
   PubMed Web of Science ®Google Scholar
• Tarner, I. H., U. Muller-Ladner, and S. Gay. 2007. Emerging targets of biologic therapies for rheumatoid arthritis. Nat. Clin. Pract. Rheumatol. 3: 336–345
   PubMedGoogle Scholar
• Clark, A. R., and J. L. Dean. 2012. The p38 MAPK pathway in rheumatoid arthritis: a sideways look. Open Rheumatol. J. 6: 209–219
   PubMedGoogle Scholar
• Goldstein, D. M., M. Soth, T. Gabriel, et al. 2011. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-p yrido[2,3-d]pyrimidin-7-one (pamapimod) and -(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]py rimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38alpha mitogen-activated protein kinase. J. Med. Chem. 54: 2255–2265
   PubMed Web of Science ®Google Scholar
• McIntyre, K. W., D. J. Shuster, K. M. Gillooly, et al. 2003. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum. 48: 2652–2659
   PubMed Web of Science ®Google Scholar
• Firestein, G. S. 2006. Inhibiting inflammation in rheumatoid arthritis. N. Engl. J. Med. 354: 80–82
   PubMedGoogle Scholar
• Yarilina, A., K. Xu, C. Chan, and L. B. Ivashkiv. 2012. Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 64: 3856–3866
   PubMed Web of Science ®Google Scholar
• Chen, Z., S. J. Kim, N. D. Chamberlain, et al. 2013. The novel role of IL-7 ligation to IL-7 receptor in myeloid cells of rheumatoid arthritis and collagen-induced arthritis. J. Immunol. 190: 5256–5266
   PubMed Web of Science ®Google Scholar
• Rubenhagen, R., J. P. Schuttrumpf, K. M. Sturmer, and K. H. Frosch. 2012. Interleukin-7 levels in synovial fluid increase with age and MMP-1 levels decrease with progression of osteoarthritis. Acta. Orthop. 83: 59–64
   PubMed Web of Science ®Google Scholar
• Bikker, A., C. E. Hack, F. P. Lafeber, and J. A. van Roon. (2012). Interleukin-7: a key mediator in T cell-driven autoimmunity, inflammation, and tissue destruction. Curr. Pharm. Des. 18: 2347–2356
   PubMed Web of Science ®Google Scholar
• Churchman, S. M., and F. Ponchel. 2008. Interleukin-7 in rheumatoid arthritis. Rheumatology (Oxford) 47: 753–759
   PubMed Web of Science ®Google Scholar
• Goeb, V., P. Aegerter, R. Parmar, et al. 2012. Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low IL-7 serum levels. Ann. Rheum. Dis. 72: 1032–1036
   PubMedGoogle Scholar
• Gonzalez-Perez, G., N. C. Segovia, A. Rivas-Carvalho, et al. 2013. Human CD4(+) effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells. Cell Mol. Immunol. 10: 261–274
   PubMedGoogle Scholar
• van Roon, J. A., K. Jacobs, S. Verstappen, et al. 2008. Reduction of serum interleukin 7 levels upon methotrexate therapy in early rheumatoid arthritis correlates with disease suppression. Ann. Rheum. Dis. 67: 1054–1055
   PubMed Web of Science ®Google Scholar
• Ji, J. D., and W. J. Lee. 2013. Interleukin-18 gene polymorphisms and rheumatoid arthritis: a meta-analysis. Gene 523: 27–32
   PubMed Web of Science ®Google Scholar
• Zhang, W., X. L. Cong, Y. H. Qin, et al. IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis. Inflammation 36: 103–109
   Google Scholar
• Volin, M. V., and A. E. Koch. 2011. Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis. J. Interferon Cytokine Res. 31: 745–751
   PubMed Web of Science ®Google Scholar
• Dai, S. M., Z. Z. Shan, H. Xu, and K. Nishioka. 2007. Cellular targets of interleukin-18 in rheumatoid arthritis. Ann. Rheum. Dis. 66: 1411–1418
   PubMedGoogle Scholar
• Gracie, J. A., S. E. Robertson, and I. B. McInnes. 2003. Interleukin-18. J. Leukoc. Biol. 73: 213–224
   PubMed Web of Science ®Google Scholar
• Petrovic-Rackov, L., and N. Pejnovic. 2006. Clinical significance of IL-18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthritis. Clin. Rheumatol. 25: 448–452
   PubMed Web of Science ®Google Scholar
• Dinarello, C. A. 2004. Interleukin-18 and the treatment of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 30: 417–434, ix
   PubMed Web of Science ®Google Scholar
• Ouyang, W., S. Rutz, N. K. Crellin, et al. 2011. Hymowitz. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Ann. Rev. Immunol. 29: 71–109
   PubMed Web of Science ®Google Scholar
• Pan, H. F., X. P. Li, S. G. Zheng, and D. Q. Ye. 2013. Emerging role of interleukin-22 in autoimmune diseases. Cytokine Growth Factor Rev. 24: 51–57
   PubMed Web of Science ®Google Scholar
• Azuma, Y. T., H. Nakajima, and T. Takeuchi. 2011. IL-19 as a potential therapeutic in autoimmune and inflammatory diseases. Curr. Pharm. Des. 17: 3776–3780
   PubMedGoogle Scholar
• Leng, R. X., H. F. Pan, J. H. Tao, and D. Q. Ye. 2011. IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. Expert Opin. Ther. Targets 15: 119–126
   PubMed Web of Science ®Google Scholar
• Mazza, G., C. A. Sabatos-Peyton, R. E. Protheroe, et al. 2010. Isolation and characterization of human interleukin-10-secreting T cells from peripheral blood. Hum. Immunol. 71: 225–234
   PubMedGoogle Scholar
• Mitchell, A., C. Rentero, Y. Endoh, et al. 2008. LILRA5 is expressed by synovial tissue macrophages in rheumatoid arthritis, selectively induces pro-inflammatory cytokines and IL-10 and is regulated by TNF-alpha, IL-10 and IFN-gamma. Eur. J. Immunol. 38: 3459–3473
   PubMedGoogle Scholar
• Liao, Y. C., W. G. Liang, F. W. Chen, et al. 2002. IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. J. Immunol. 169: 4288–4297
   PubMed Web of Science ®Google Scholar
• Hsu, Y. H., P. P. Hsieh, and M. S. Chang. 2012. Interleukin-19 blockade attenuates collagen-induced arthritis in rats. Rheumatology (Oxford) 51: 434–442
   PubMed Web of Science ®Google Scholar
• Sakurai, N., T. Kuroiwa, H. Ikeuchi, et al. 2008. Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation. Rheumatology (Oxford) 47: 815–820
   PubMed Web of Science ®Google Scholar
• Hsing, C. H., M. Y. Hsieh, W. Y. Chen, et al. 2006. Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass. Ann. Thorac. Surg. 81: 2196–2201
   PubMedGoogle Scholar
• Logsdon, N. J., A. Deshpande, B. D. Harris, et al. 2012. Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines. Proc. Natl. Acad. Sci. U S A 109: 12704–12709
   PubMedGoogle Scholar
• van Hamburg, J. P., O. B. Corneth, S. M. Paulissen, et al. 2013. IL-17/Th17 mediated synovial inflammation is IL-22 independent. Ann. Rheum. Dis. 72: 1700–1707
   PubMed Web of Science ®Google Scholar
• Xie, Q., S. C. Wang, and J. Li. 2012. Interleukin 22, a potential therapeutic target for rheumatoid arthritis. J. Rheumatol. 39: 2220; author reply 2221
   PubMedGoogle Scholar
• Mitra, A., S. K. Raychaudhuri, and S. P. Raychaudhuri. 2012. Functional role of IL-22 in psoriatic arthritis. Arthritis Res. Ther. 14: R65
   PubMed Web of Science ®Google Scholar
• da Rocha, L. F., Jr., A. L. Duarte, A. T. Dantas, et al. 2012. Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity. J. Rheumatol. 39: 1320–1325
   PubMed Web of Science ®Google Scholar
• Kim, K. W., H. R. Kim, J. Y. Park, et al. 2012. Interleukin-22 promotes osteoclastogenesis in rheumatoid arthritis through induction of RANKL in human synovial fibroblasts. Arthritis Rheum. 64: 1015–1023
   PubMed Web of Science ®Google Scholar
• Mitra, A., S. K. Raychaudhuri, and S. P. 2012. Raychaudhuri. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine 60: 38–42
   Google Scholar
• Zhang, L., J. M. Li, X. G. Liu, et al. 2011. Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J. Clin. Immunol. 31: 606–614
   PubMed Web of Science ®Google Scholar
• Leipe, J., M. A. Schramm, M. Grunke, et al. 2011. Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis. Ann. Rheum. Dis. 70: 1453–1457
   PubMed Web of Science ®Google Scholar
• Zhang, L., Y. G. Li, Y. H. Li, et al. 2012. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS One 7: e31000
   PubMed Web of Science ®Google Scholar
• Ikeuchi, H., T. Kuroiwa, N. Hiramatsu, et al. 2005. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 52: 1037–1046
   PubMed Web of Science ®Google Scholar
• Marijnissen, R. J., M. I. Koenders, R. L. Smeets, et al. 2011. Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradation. Arthritis Rheum. 63: 2939–2948
   PubMedGoogle Scholar
• van de Veerdonk, F. L., B. Lauwerys, R. J. Marijnissen, et al. 2011. The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum. 63: 1507–1516
   PubMedGoogle Scholar
• Liang, S. C., X. Y. Tan, D. P. Luxenberg, et al. 2006. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203: 2271–2279
   PubMed Web of Science ®Google Scholar
• Moon, Y. M., B. Y. Yoon, Y. M. Her, et al. 2012. IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis in rheumatoid arthritis. Arthritis Res. Ther. 14: R246 . doi:10.1186/ar4089
   PubMed Web of Science ®Google Scholar
• Xu, W. D., M. Zhang, C. C. Feng, et al. 2013. IL-32 with potential insights into rheumatoid arthritis. Clin. Immunol. 147: 89–94
   PubMed Web of Science ®Google Scholar
• Gui, M., H. Zhang, K. Zhong, et al. 2013. Clinical significance of interleukin-32 expression in patients with rheumatoid arthritis. Asian Pac. J. Allergy Immunol. 31: 73–78
   PubMedGoogle Scholar
• Jeong, H. J., S. Y. Nam, H. A. Oh, et al. 2012. Interleukin-32-induced thymic stromal lymphopoietin plays a critical role in macrophage differentiation through the activation of caspase-1 in vitro. Arthritis Res. Ther. 14: R259 . doi:10.1186/ar4104
   Google Scholar
• Park, Y. E., G. T. Kim, S. G. Lee, et al. 2013. IL-32 aggravates synovial inflammation and bone destruction and increases synovial natural killer cells in experimental arthritis models. Rheumatol. Int. 33: 671–679
   PubMedGoogle Scholar
• Kim, Y. G., C. K. Lee, J. S. Oh, et al. 2010. Effect of interleukin-32gamma on differentiation of osteoclasts from CD14+ monocytes. Arthritis Rheum. 62: 515–523
   PubMed Web of Science ®Google Scholar
• Netea, M. G., T. Azam, G. Ferwerda, et al. 2005. IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. Proc. Natl. Acad. Sci. U S A 102: 16309–16314
   PubMed Web of Science ®Google Scholar
• Heinhuis, B., M. G. Netea, W. B. van den Berg, et al. 2012. Interleukin-32: a predominantly intracellular proinflammatory mediator that controls cell activation and cell death. Cytokine 60: 321–327
   PubMed Web of Science ®Google Scholar
• Joosten, L. A., M. G. Netea, S. H. Kim, et al. 2006. IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc. Natl. Acad. Sci. U S A 103: 3298–3303
   PubMed Web of Science ®Google Scholar
• Lago, F., C. Dieguez, J. Gomez-Reino, and O. Gualillo. 2007. Adipokines as emerging mediators of immune response and inflammation. Nat. Clin. Pract. Rheumatol. 3: 716–724
   PubMedGoogle Scholar
• El-Hini, S. H., F. I. Mohamed, A. A. Hassan, et al. 2013. Visfatin and adiponectin as novel markers for evaluation of metabolic disturbance in recently diagnosed rheumatoid arthritis patients. Rheumatol Int. 33: 2283–2289
   PubMed Web of Science ®Google Scholar
• Fadda, S. M., S. M. Gamal, N. Y. Elsaid, and A. M. Mohy. 2013. Resistin in inflammatory and degenerative rheumatologic diseases: relationship between resistin and rheumatoid arthritis disease progression. Z. Rheumatol. 72: 594–600
   PubMedGoogle Scholar
• Frommer, K. W., A. Schaffler, C. Buchler, et al. 2012. Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis? Ann. Rheum. Dis. 71: 1724–1732
   PubMed Web of Science ®Google Scholar
• Conde, J., M. Scotece, V. Lopez, et al. 2012. Adiponectin and leptin induce VCAM-1 expression in human and murine chondrocytes. PLoS One 7: e52533
   PubMed Web of Science ®Google Scholar
• De Sanctis, J. B., M. Zabaleta, N. E. Bianco, et al. 2009. Serum adipokine levels in patients with systemic lupus erythematosus. Autoimmunity 42: 272–274
   PubMed Web of Science ®Google Scholar
• Hui, W., G. J. Litherland, M. S. Elias, et al. 2012. Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Ann. Rheum. Dis. 71: 455–462
   PubMed Web of Science ®Google Scholar
• Otero, M., R. Lago, R. Gomez, et al. 2006. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann. Rheum. Dis. 65: 1198–1201
   PubMed Web of Science ®Google Scholar
• Toussirot, E., G. Streit, and D. Wendling. 2007. The contribution of adipose tissue and adipokines to inflammation in joint diseases. Curr. Med. Chem. 14: 1095–1100
   PubMed Web of Science ®Google Scholar
• Bernotiene, E., G. Palmer, and C. Gabay. 2006. The role of leptin in innate and adaptive immune responses. Arthritis Res. Ther. 8: 217 . doi: 10.1186/ar2004
   PubMed Web of Science ®Google Scholar
• Gualillo, O. 2007. Further evidence for leptin involvement in cartilage homeostases. Osteoarthritis Cartilage 15: 857–860
   PubMedGoogle Scholar
• Otero, M., R. Lago, F. Lago, et al. 2005. Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1. Arthritis Res. Ther. 7: R581–591
   PubMed Web of Science ®Google Scholar
• Otvos, L., Jr. W. H. Shao, A. S. Vanniasinghe, et al. 2011. Toward understanding the role of leptin and leptin receptor antagonism in preclinical models of rheumatoid arthritis. Peptides 32: 1567–1574
   PubMedGoogle Scholar
• Rose, D. P., E. M. Gilhooly, and D. W. Nixon. 2002. Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review). Int. J. Oncol. 21: 1285–1292
   PubMed Web of Science ®Google Scholar
• Iliopoulos, D., K. N. Malizos, and A. Tsezou. 2007. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann. Rheum. Dis. 66: 1616–1621
   PubMed Web of Science ®Google Scholar
• Anders, H. J., M. Rihl, A. Heufelder, et al. 1999. Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. Metabolism 48: 745–748
   PubMed Web of Science ®Google Scholar
• Hizmetli, S., M. Kisa, N. Gokalp, and M. Z. Bakici. 2007. Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int. 27: 335–338
   PubMedGoogle Scholar
• Gunaydin, R., T. Kaya, A. Atay, et al. 2006. Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med. J. 99: 1078–1083
   PubMed Web of Science ®Google Scholar
• Olama, S. M., M. K. Senna, and M. Elarman. 2012. Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol. Int. 32: 683–690
   PubMed Web of Science ®Google Scholar
• Popa, C., M. G. Netea, T. R. Radstake, et al. 2005. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann. Rheum. Dis. 64: 1195–1198
   PubMed Web of Science ®Google Scholar
• Chen, X., J. Lu, J. Bao, et al. 2013. Adiponectin: a biomarker for rheumatoid arthritis? Cytokine Growth Factor Rev. 24: 83–89
   PubMedGoogle Scholar
• Ozgen, M., S. S. Koca, N. Dagli, et al. 2010. Serum adiponectin and vaspin levels in rheumatoid arthritis. Arch. Med. Res. 41: 457–463
   PubMed Web of Science ®Google Scholar
• Schaffler, A., A. Ehling, E. Neumann, et al. 2003. Adipocytokines in synovial fluid. JAMA 290: 1709–1710
   PubMed Web of Science ®Google Scholar
• Ehling, A., A. Schaffler, H. Herfarth, et al. 2006. The potential of adiponectin in driving arthritis. J. Immunol. 176: 4468–4478
   PubMed Web of Science ®Google Scholar
• Targonska-Stepniak, B., M. Dryglewska, and M. Majdan. 2010. Adiponectin and leptin serum concentrations in patients with rheumatoid arthritis. Rheumatol Int. 30: 731–737
   PubMed Web of Science ®Google Scholar
• Senolt, L., D. Housa, Z. Vernerova, et al. 2007. Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann. Rheum. Dis. 66: 458–463
   PubMed Web of Science ®Google Scholar
• Bokarewa, M., I. Nagaev, L. Dahlberg, et al. 2005. Resistin, an adipokine with potent proinflammatory properties. J. Immunol. 174: 5789–5795
   PubMed Web of Science ®Google Scholar
• McTernan, P. G., C. M. Kusminski, and S. Kumar. 2006. Resistin. Curr. Opin. Lipidol. 17: 170–175
   PubMed Web of Science ®Google Scholar
• Lehrke, M., M. P. Reilly, S. C. Millington, et al. 2004. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 1: e45
   PubMed Web of Science ®Google Scholar
• Verma, S., S. H. Li, C. H. Wang, et al. 2003. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108: 736–740
   PubMed Web of Science ®Google Scholar
• Matsui, H., A. Tsutsumi, M. Sugihara, et al. 2008. Visfatin (pre-B cell colony-enhancing factor) gene expression in patients with rheumatoid arthritis. Ann. Rheum. Dis. 67: 571–572
   PubMedGoogle Scholar
• Finnegan, A., S. Ashaye, and K. M. Hamel. 2012. B effector cells in rheumatoid arthritis and experimental arthritis. Autoimmunity 45: 353–363
   PubMed Web of Science ®Google Scholar
• Nowell, M. A., P. J. Richards, C. A. Fielding, et al. 2006. Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis. Arthritis Rheum. 54: 2084–2095
   PubMed Web of Science ®Google Scholar
• Moschen, A. R., A. Kaser, B. Enrich, et al. 2007. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J. Immunol. 178: 1748–1758
   PubMed Web of Science ®Google Scholar
• Nienhuis, H. L., J. Westra, A. J. Smit, et al. 2009. AGE and their receptor RAGE in systemic autoimmune diseases: an inflammation propagating factor contributing to accelerated atherosclerosis. Autoimmunity 42: 302–304
   PubMed Web of Science ®Google Scholar
• Santilli, F., N. Vazzana, L. G. Bucciarelli, and G. Davi. 2009. Soluble forms of RAGE in human diseases: clinical and therapeutical implications. Curr. Med. Chem. 16: 940–952
   PubMed Web of Science ®Google Scholar
• Avalos, A. M., K. Kiefer, J. Tian, et al. 2010. RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes. Autoimmunity 43: 103–110
   Google Scholar
• Rasheed, Z., and T. M. Haqqi. 2012. Endoplasmic reticulum stress induces the expression of COX-2 through activation of eIF2alpha, p38-MAPK and NF-kappaB in advanced glycation end products stimulated human chondrocytes. Biochim Biophys Acta 1823: 2179–2189
   Google Scholar
• Riehl, A., J. Nemeth, P. Angel, and J. Hess. 2009. The receptor RAGE: bridging inflammation and cancer. Cell Commun. Signal. 7: 12
   PubMed Web of Science ®Google Scholar
• Sunahori, K., M. Yamamura, J. Yamana, et al. 2006. Increased expression of receptor for advanced glycation end products by synovial tissue macrophages in rheumatoid arthritis. Arthritis Rheum. 54: 97–104
   PubMed Web of Science ®Google Scholar
• Paunovic, V., and M. M. Harnett. 2013. Mitogen-activated protein kinases as therapeutic targets for rheumatoid arthritis. Drugs 73: 101–115
   PubMed Web of Science ®Google Scholar
• Chakravarty, S. D., P. I. Poulikakos, L. B. Ivashkiv, et al. 2013. Kinase inhibitors: a new tool for the treatment of rheumatoid arthritis. Clin. Immunol. 148: 66–78
   PubMed Web of Science ®Google Scholar
• Kyttaris, V. C. 2012. Kinase inhibitors: a new class of antirheumatic drugs. Drug Des. Dev. Ther. 6: 245–250
   PubMed Web of Science ®Google Scholar
• Abu-Amer, Y., I. Darwech, and J. Otero. 2008. Role of the NF-kappaB axis in immune modulation of osteoclasts and bone loss. Autoimmunity 41: 204–211
   PubMed Web of Science ®Google Scholar
• van Loo, G., and R. Beyaert. 2011. Negative regulation of NF-kappaB and its involvement in rheumatoid arthritis. Arthritis Res. Ther. 13: 221
   PubMed Web of Science ®Google Scholar
• Aupperle, K. R., Y. Yamanishi, B. L. Bennett, et al. 2001. Expression and regulation of inducible IkappaB kinase (IKK-i) in human fibroblast-like synoviocytes. Cell Immunol. 214: 54–59
   PubMedGoogle Scholar
• Nagineni, C. N., R. K. Kutty, B. Detrick, and J. J. Hooks. 1996. Inflammatory cytokines induce intercellular adhesion molecule-1 (ICAM-1) mRNA synthesis and protein secretion by human retinal pigment epithelial cell cultures. Cytokine 8: 622–630
   PubMed Web of Science ®Google Scholar
• Tak, P. P., D. M. Gerlag, K. R. Aupperle, et al. 2001. Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum. 44: 1897–1907
   PubMed Web of Science ®Google Scholar
• Andreakos, E., C. Smith, S. Kiriakidis, et al. 2003. Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapy. Arthritis Rheum. 48: 1901–1912
   Google Scholar
• Jue, D. M., K. I. Jeon, and J. Y. Jeong. 1999. Nuclear factor kappaB (NF-kappaB) pathway as a therapeutic target in rheumatoid arthritis. J. Korean Med. Sci. 14: 231–238
   PubMedGoogle Scholar
• Han, Z., D. L. Boyle, A. M. Manning, and G. S. Firestein. 1998. AP-1 and NF-kappaB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28: 197–208
   PubMed Web of Science ®Google Scholar
• Roman-Blas, J. A., and S. A. Jimenez. 2006. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage 14: 839–848
   PubMed Web of Science ®Google Scholar
• Egan, P. J., K. E. Lawlor, W. S. Alexander, and I. P. Wicks. 2003. Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J. Clin. Invest. 111: 915–924
   PubMed Web of Science ®Google Scholar
• Wong, P. K., P. J. Egan, B. A. Croker, et al. 2006. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J. Clin. Invest. 116: 1571–1581
   PubMed Web of Science ®Google Scholar
• Shouda, T., T. Yoshida, T. Hanada, et al. 2001. Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J. Clin. Invest. 108: 1781–1788
   PubMed Web of Science ®Google Scholar
• Rosengren, S., M. Corr, G. S. Firestein, and D. L. Boyle. The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type I interferon. Ann. Rheum. Dis. 71: 440–447
   Google Scholar
• La Cava, A. 2011. Regulatory immune cell subsets in autoimmunity. Autoimmunity 44: 1–2
   PubMed Web of Science ®Google Scholar
• Marino, E., and S. T. Grey. 2012. B cells as effectors and regulators of autoimmunity. Autoimmunity 45: 377–387
   PubMed Web of Science ®Google Scholar
• Schett, G. 2008. Review: immune cells and mediators of inflammatory arthritis. Autoimmunity 41: 224–229
   PubMed Web of Science ®Google Scholar
• Mannoor, K., Y. Xu, and C. Chen. 2013. Natural autoantibodies and associated B cells in immunity and autoimmunity. Autoimmunity 46: 138–147
   PubMed Web of Science ®Google Scholar
• Lee, A. N., C. E. Beck, and M. Hall. 2008. Rheumatoid factor and anti-CCP autoantibodies in rheumatoid arthritis: a review. Clin. Lab. Sci. 21: 15–18
   PubMedGoogle Scholar
• Huang, Q. Q., R. E. Koessler, R. Birkett, et al. 2012. Glycoprotein 96 perpetuates the persistent inflammation of rheumatoid arthritis. Arthritis Rheum. 64: 3638–3648
   PubMedGoogle Scholar
• Ramirez-Herraiz, E., V. Escudero-Vilaplana, E. Alanon-Plaza, et al. 2013. Efficiency of adalimumab, etanercept and infliximab in rheumatoid arthritis patients: dosing patterns and effectiveness in daily clinical practice. Clin. Exp. Rheumatol. 31: 559–565
   PubMed Web of Science ®Google Scholar
• Kurz, K., M. Herold, C. Winkler, et al. 2011. Effects of adalimumab therapy on disease activity and interferon-gamma-mediated biochemical pathways in patients with rheumatoid arthritis. Autoimmunity 44: 235–242
   PubMed Web of Science ®Google Scholar
• Ruiz Garcia, V., P. Jobanputra, A. Burls, et al. 2011. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Cochrane Database Syst. Rev. CD007649
   Google Scholar
• Rubbert-Roth, A., and A. Perniok. 2003. Interleukin-1 receptor antagonist anakinra (Kineret) for treatment of rheumatic arthritis. Z. Rheumatol. 62: 367–377
   PubMedGoogle Scholar
• Alten, R., J. Gomez-Reino, P. Durez, et al. 2011. Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. BMC Musculoskelet. Disord. 12: 153
   PubMed Web of Science ®Google Scholar
• Ratner, M. 2008. IL-1 trap go-ahead. Nat. Biotechnol. 26: 485
   PubMedGoogle Scholar
• Singh, J. A., S. Beg, and M. A. Lopez-Olivo. 2010. Tocilizumab for rheumatoid arthritis. Cochrane Database Syst. Rev. CD008331
   Google Scholar
• Metz, S., M. Wiesinger, M. Vogt, et al. 2007. Characterization of the Interleukin (IL)-6 Inhibitor IL-6-RFP: fused receptor domains act as high affinity cytokine-binding proteins. J. Biol. Chem. 282: 1238–1248
   PubMed Web of Science ®Google Scholar
• Itano, A. A., M. J. Sims, and G. Siu. Mechanistic medicine: novel strategies for clinical trials. Autoimmunity 43: 560–571
   Google Scholar
• Baslund, B., N. Tvede, B. Danneskiold-Samsoe, et al. 2005. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum. 52: 2686–2692
   PubMed Web of Science ®Google Scholar
• Kim, Y. S., W. Maslinski, X. X. Zheng, et al. 1998. Targeting the IL-15 receptor with an antagonist IL-15 mutant/Fc gamma2a protein blocks delayed-type hypersensitivity. J. Immunol. 160: 5742–5748
   PubMed Web of Science ®Google Scholar
• Hueber, W., D. D. Patel, T. Dryja, et al. 2010. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci. Transl. Med. 2: 52ra72
   PubMed Web of Science ®Google Scholar
• Bush, K. A., K. M. Farmer, J. S. Walker, and B. W. Kirkham. 2002. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 46: 802–805
   PubMed Web of Science ®Google Scholar
• Billich, A. 2007. Drug evaluation: apilimod, an oral IL-12/IL-23 inhibitor for the treatment of autoimmune diseases and common variable immunodeficiency. IDrugs 10: 53–59
   PubMed Web of Science ®Google Scholar
• Wada, Y., R. Lu, D. Zhou, et al. 2007. Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood 109: 1156–1164
   PubMed Web of Science ®Google Scholar
• Hartgring, S. A., C. R. Willis, D. Alcorn, et al. 2010. Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators. Arthritis Rheum. 62: 2716–2725
   PubMedGoogle Scholar
• Otvos, L., Jr., W. H. Shao, A. S. Vanniasinghe, et al. 2011. Toward understanding the role of leptin and leptin receptor antagonism in preclinical models of rheumatoid arthritis. Peptides 32: 1567–1574
   PubMedGoogle Scholar
• Arumugam, T., V. Ramachandran, S. B. Gomez, et al. 2012. S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin. Cancer Res. 18: 4356–4364
   PubMed Web of Science ®Google Scholar
• Marsche, G., B. Weigle, W. Sattler, and E. Malle. 2007. Soluble RAGE blocks scavenger receptor CD36-mediated uptake of hypochlorite-modified low-density lipoprotein. FASEB J. 21: 3075–3082
   PubMed Web of Science ®Google Scholar
• Rasheed, Z., N. Akhtar, and T. M. Haqqi. Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-kappaB in human osteoarthritis chondrocytes. Rheumatology (Oxford) 50: 838–851
   Google Scholar
• Steenvoorden, M. M., R. E. Toes, H. K. Ronday, et al. 2007. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro. Clin. Exp. Rheumatol. 25: 740–742
   PubMed Web of Science ®Google Scholar
• McCormack, P. L. 2011. Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Drugs 71: 2457–2489
   PubMed Web of Science ®Google Scholar
• Chiba, A., M. Mizuno, C. Tomi, et al. 2012. A 4-trifluoromethyl analogue of celecoxib inhibits arthritis by suppressing innate immune cell activation. Arthritis Res. Ther. 14: R9
   Google Scholar
• You, X., M. Pan, W. Gao, et al. 2006. Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response. Arthritis Rheum. 54: 877–886
   PubMedGoogle Scholar
• Anderson, A. E., A. R. Lorenzi, A. Pratt, et al. 2012. Immunity 12 years after alemtuzumab in RA: CD5(+) B-cell depletion, thymus-dependent T-cell reconstitution and normal vaccine responses. Rheumatology (Oxford) 51: 1397–1406
   PubMedGoogle Scholar
• Bugelski, P. J., D. J. Herzyk, S. Rehm, et al. 2000. Preclinical development of keliximab, a Primatized anti-CD4 monoclonal antibody, in human CD4 transgenic mice: characterization of the model and safety studies. Hum. Exp. Toxicol. 19: 230–243
   PubMed Web of Science ®Google Scholar
• Mould, D. R., C. B. Davis, E. A. Minthorn, et al. 1999. A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in patients with rheumatoid arthritis. Clin. Pharmacol. Ther. 66: 246–257
   PubMed Web of Science ®Google Scholar
• Genovese, M. C., J. L. Kaine, M. B. Lowenstein, et al. 2008. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum. 58: 2652–2661
   PubMed Web of Science ®Google Scholar
• Ostergaard, M., B. Baslund, W. Rigby, et al. 2010. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum. 62: 2227–2238
   PubMed Web of Science ®Google Scholar
• Rubbert-Roth, A. 2010. TRU-015, a fusion protein derived from an anti-CD20 antibody, for the treatment of rheumatoid arthritis. Curr. Opin. Mol. Ther. 12: 115–123
   PubMedGoogle Scholar
• Westra, J., P. C. Limburg, P. de Boer, and M. H. van Rijswijk. 2004. Effects of RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts. Ann. Rheum. Dis. 63: 1453–1459
   PubMed Web of Science ®Google Scholar
• Wadsworth, S. A., D. E. Cavender, S. A. Beers, et al. 1999. RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. J. Pharmacol. Exp. Ther. 291: 680–687
   PubMed Web of Science ®Google Scholar
• Montalban, A. G., E. Boman, C. D. Chang, et al. 2010. KR-003048, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. Eur J. Pharmacol. 632: 93–102
   PubMed Web of Science ®Google Scholar
• Nishikawa, M., A. Myoui, T. Tomita, et al. 2003. Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 48: 2670–2681
   PubMed Web of Science ®Google Scholar
• Haddad, J. J. 2001. VX-745. Vertex pharmaceuticals. Curr. Opin. Investig. Drugs 2: 1070–1076
   PubMedGoogle Scholar
• Damjanov, N., R. S. Kauffman, and G. T. Spencer-Green. 2009. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 60: 1232–1241
   PubMed Web of Science ®Google Scholar
• Lindstrom, T. M., and W. H. Robinson. 2010. A multitude of kinases–which are the best targets in treating rheumatoid arthritis? Rheum. Dis. Clin. North Am. 36: 367–383
   PubMed Web of Science ®Google Scholar
• Page, T. H., A. Brown, E. M. Timms, et al. Inhibitors of p38 suppress cytokine production in rheumatoid arthritis synovial membranes: does variable inhibition of interleukin-6 production limit effectiveness in vivo? Arthritis Rheum. 62: 3221–3231
   Google Scholar
• Han, Z., D. L. Boyle, L. Chang, et al. 2001. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J. Clin. Invest. 108: 73–81
   PubMed Web of Science ®Google Scholar
• Heo, Y. S., S. K. Kim, C. I. Seo, et al. 2004. Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125. EMBO J. 23: 2185–2195
   PubMed Web of Science ®Google Scholar
• Ohori, M., M. Takeuchi, R. Maruki, et al. 2007. FR180204, a novel and selective inhibitor of extracellular signal-regulated kinase, ameliorates collagen-induced arthritis in mice. Naunyn Schmiedebergs Arch. Pharmacol. 374: 311–316
   PubMed Web of Science ®Google Scholar
• Hotokezaka, H., E. Sakai, K. Kanaoka, et al. 2002. U0126 and PD98059, specific inhibitors of MEK, accelerate differentiation of RAW264.7 cells into osteoclast-like cells. J. Biol. Chem. 277: 47366–47372
   PubMed Web of Science ®Google Scholar
• Thiel, M. J., C. J. Schaefer, M. E. Lesch, et al. 2007. Central role of the MEK/ERK MAP kinase pathway in a mouse model of rheumatoid arthritis: potential proinflammatory mechanisms. Arthritis Rheum. 56: 3347–3357
   PubMedGoogle Scholar
• Singh, K., P. Deshpande, S. Pryshchep, et al. 2009. ERK-dependent T cell receptor threshold calibration in rheumatoid arthritis. J. Immunol. 183: 8258–8267
   PubMed Web of Science ®Google Scholar
• Fujihara, S. M., J. S. Cleaveland, L. S. Grosmaire, et al. 2000. A D-amino acid peptide inhibitor of NF-kappa B nuclear localization is efficacious in models of inflammatory disease. J. Immunol. 165: 1004–1012
   PubMed Web of Science ®Google Scholar
• McIntyre, K. W., D. J. Shuster, K. M. Gillooly, et al. 2003. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum. 48: 2652–2659
   PubMed Web of Science ®Google Scholar
• Gillooly, K. M., M. A. Pattoli, T. L. Taylor, et al. 2009. Periodic, partial inhibition of IkappaB Kinase beta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis. J. Pharmacol. Exp. Ther. 331: 349–360
   PubMedGoogle Scholar
• Hammaker, D., S. Sweeney, and G. S. Firestein. 2003. Signal transduction networks in rheumatoid arthritis. Ann. Rheum. Dis. 62: ii86–89
   PubMedGoogle Scholar
• Peet, G. W., and J. Li. 1999. IkappaB kinases alpha and beta show a random sequential kinetic mechanism and are inhibited by staurosporine and quercetin. J. Biol. Chem. 274: 32655–32661
   PubMed Web of Science ®Google Scholar
• Podolin, P. L., J. F. Callahan, B. J. Bolognese, et al. 2005. Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation. J. Pharmacol. Exp. Ther. 312: 373–381
   PubMed Web of Science ®Google Scholar
• Mbalaviele, G., C. D. Sommers, S. L. Bonar, et al. 2009. A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models. J. Pharmacol. Exp. Ther. 329: 14–25
   PubMedGoogle Scholar
• Schopf, L., A. Savinainen, K. Anderson, et al. 2006. IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. Arthritis Rheum. 54: 3163–3173
   PubMed Web of Science ®Google Scholar
• Okazaki, Y., T. Sawada, K. Nagatani, et al. 2005. Effect of nuclear factor-kappaB inhibition on rheumatoid fibroblast-like synoviocytes and collagen induced arthritis. J. Rheumatol. 32: 1440–1447
   PubMed Web of Science ®Google Scholar
• Weber, C. K., S. Liptay, T. Wirth, et al. 2000. Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology 119: 1209–1218
   PubMed Web of Science ®Google Scholar
• Kishore, N., C. Sommers, S. Mathialagan, et al. 2003. A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J. Biol. Chem. 278: 32861–32871
   PubMed Web of Science ®Google Scholar
• Meyer, S., N. G. Kohler, and A. Joly. 1997. Cyclosporine A is an uncompetitive inhibitor of proteasome activity and prevents NF-kappaB activation. FEBS Lett. 413: 354–358
   PubMed Web of Science ®Google Scholar
• Venkataraman, L., S. J. Burakoff, and R. Sen. 1995. FK506 inhibits antigen receptor-mediated induction of c-rel in B and T lymphoid cells. J. Exp. Med. 181: 1091–1099
   PubMedGoogle Scholar
• Kawakami, A., T. Nakashima, H. Sakai, et al. 1999. Regulation of synovial cell apoptosis by proteasome inhibitor. Arthritis Rheum. 42: 2440–2448
   PubMed Web of Science ®Google Scholar
• Yamaoka, K., and Y. Tanaka. 2009. Jak inhibitor; possibility and mechanism as a new disease modifying anti-rheumatic drug. Nihon Rinsho Meneki Gakkai Kaishi. 32: 85–91
   PubMedGoogle Scholar
• Senolt, L., J. Vencovsky, K. Pavelka, et al. 2009. Prospective new biological therapies for rheumatoid arthritis. Autoimmun. Rev. 9: 102–107
   PubMed Web of Science ®Google Scholar
• Anitua, E., M. Sanchez, G. Orive, and S. Padilla. 2013. A biological therapy to osteoarthritis treatment using platelet-rich plasma. Expert Opin. Biol. Ther. 13: 1161–1172
   PubMed Web of Science ®Google Scholar
• Abramson, S. B., and Y. Yazici. 2006. Biologics in development for rheumatoid arthritis: relevance to osteoarthritis. Adv. Drug Deliv. Rev. 58: 212–225
   PubMed Web of Science ®Google Scholar
• Chevalier, X., F. Eymard, and P. Richette. 2013. Biologic agents in osteoarthritis: hopes and disappointments. Nat. Rev. Rheumatol. 9: 400–410
   PubMed Web of Science ®Google Scholar
• Rifkin, L. M., A. D. Birnbaum, and D. A. Goldstein. 2013. TNF inhibition for ophthalmic indications: current status and outlook. BioDrugs. 27: 347–357
   PubMed Web of Science ®Google Scholar