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Review

Small-molecule inhibitors and the salivary gland epithelium in Sjögren’s syndrome

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Pages 605-616 | Received 27 Mar 2019, Accepted 11 Jun 2019, Published online: 16 Jun 2019

References

  • Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League against Rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017;76:9–16.
  • Hjelmervik TOR, Petersen K, Jonassen I, et al. Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren’s syndrome patients from healthy control subjects. Arthritis Rheum. 2005;52:1534–1544.
  • Gottenberg J-E, Cagnard N, Lucchesi C, et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren’s syndrome. Proc Natl Acad Sci U S A. 2006;103:2770–2775.
  • Haupl T, Biesen R, Smiljanovic B, et al. The type 1 interferon signature: facts, fads and fallacies. Ann Rheum Dis. 2011;70:A24–A24.
  • Igoe A, Scofield RH. Autoimmunity and infection in Sjögren’s syndrome. Curr Opin Rheumatol. 2013;25:480–487.
  • Nakayamada S, Tanaka Y. BAFF- and APRIL-targeted therapy in systemic autoimmune diseases. Inflamm Regen. 2016;36:6.
  • Pijpe J, Kalk WWI, Bootsma H, et al. Progression of salivary gland dysfunction in patients with Sjögren’s syndrome. Ann Rheum Dis. 2007;66:107–112.
  • Gannot G, Lancaster HE, Fox PC. Clinical course of primary Sjögren’s syndrome: salivary, oral, and serologic aspects. J Rheumatol. 2000;27:1905–1909.
  • Jonsson R, Kroneld U, Backman K, et al. Progression of sialadenitis in Sjögren’s sydrome. Br J Rheumatol. 1993;32:578–581.
  • Teos LY, Zhang Y, Cotrim AP, et al. IP3R deficit underlies loss of salivary fluid secretion in Sjögren’s syndrome. Sci Rep. 2015;5:13953.
  • Ambudkar IS. Ca2+ signaling and regulation of fluid secretion in salivary gland acinar cells. Cell Calcium. 2014;55:297.
  • Perl A. Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases. Nat Rev Rheumatol. 2016;12:169–182.
  • Villarino AV, Kanno Y, Ferdinand JR, et al. Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol. 2015;194:21–27.
  • O’Shea JJ, Kontzias A, Yamaoka K, et al. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72(Suppl 2):ii111–5.
  • Gadina M, Gazaniga N, Vian L, et al. Small molecules to the rescue: inhibition of cytokine signaling in immune-mediated diseases. J Autoimmun. 2017;85:20–31.
  • Ong HL, Subedi KP, Son G-Y, et al. Tuning store-operated calcium entry to modulate Ca2+-dependent physiological processes. Biochim Biophys Acta - Mol Cell Res. 2019;1866:1037–1045.
  • Aure MH, Konieczny SF, Ovitt CE. Salivary gland homeostasis is maintained through acinar cell self-duplication. Dev Cell. 2015;33:231–237.
  • Pringle S, Maimets M, van der Zwaag M, et al. Human salivary gland stem cells functionally restore radiation damaged salivary glands. Stem Cells. 2016;34:640–652.
  • Dimitriou ID, Kapsogeorgou EK, Abu-Helu RF, et al. Establishment of a convenient system for the long-term culture and study of non-neoplastic human salivary gland epithelial cells. Eur J Oral Sci. 2002;110:21–30.
  • Pringle S, Wang X, Verstappen GMPJ, et al. Salivary gland stem cells age prematurely in primary Sjögren’s syndrome. Arthritis Rheumatol. 2019;71:133–142.
  • Clevers H. Modeling development and disease with organoids. Cell. 2016;165:1586–1597.
  • Routsias JG, Tzioufas AG. Autoimmune response and target autoantigens in Sjogren’s syndrome. Eur J Clin Invest. 2010;40:1026–1036.
  • Manoussakis MN, Spachidou MP, Maratheftis CI. Salivary epithelial cells from Sjogren’s syndrome patients are highly sensitive to anoikis induced by TLR-3 ligation. J Autoimmun. 2010;35:212–218.
  • Varin -M-M, Guerrier T, Devauchelle-Pensec V, et al. In Sjögren’s syndrome, B lymphocytes induce epithelial cells of salivary glands into apoptosis through protein kinase C delta activation. Autoimmun Rev. 2012;11:252–258.
  • Ohlsson M, Jonsson R, Brokstad KA. Subcellular Redistribution and. Surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjogren’s syndrome. Scand J Immunol. 2002;56:456–469.
  • Lisi S, Sisto M, Lofrumento D, et al. Regulation of mRNA caspase-8 levels by anti-nuclear autoantibodies. Clin Exp Med. 2010;10:199–203.
  • Sisto M, Lisi S, Lofrumento D, et al. Autoantibodies from Sjögren’s syndrome trigger apoptosis in salivary gland cell line. Ann N Y Acad Sci. 2007;1108:418–425.
  • Blokland SLM, Hillen MR, Wichers CGK, et al. Increased mTORC1 activation in salivary gland B cells and T cells from patients with Sjögren’s syndrome: mTOR inhibition as a novel therapeutic strategy to halt immunopathology? RMD Open. 2019;5:e000701.
  • Soypaçacı Z, Gümüş ZZ, Çakaloğlu F, et al. Role of the mTOR pathway in minor salivary gland changes in Sjogren’s syndrome and systemic sclerosis. Arthritis Res Ther. 2018;20:170.
  • Manoussakis MN, Moutsopoulos HM. Sjögren’s syndrome: autoimmune epithelitis. Best Pract Res Clin Rheumatol. 2000;14:73–95.
  • Manoussakis MN, Kapsogeorgou EK. The role of intrinsic epithelial activation in the pathogenesis of Sjögren’s syndrome. J Autoimmun. 2010;35:219–224.
  • Ohlsson M, Szodoray P, Loro LL, et al. CD40, CD154, Bax and Bcl-2 expression in Sjogren’s syndrome salivary glands: a putative anti-apoptotic role during its effector phases. Scand J Immunol. 2002;56:561–571.
  • Sakai A, Sugawara Y, Kuroishi T, et al. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjögren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008;181:2898–2906.
  • Szyszko EA, Brokstad KA, Oijordsbakken G, et al. Salivary glands of primary Sjögren’s syndrome patients express factors vital for plasma cell survival. Arthritis Res Ther. 2011;13:R2.
  • Sfriso P, Oliviero F, Calabrese F, et al. Epithelial CXCR3-B regulates chemokines bioavailability in normal, but not in Sjogren’s syndrome, salivary glands. J Immunol. 2006;176:2581–2589.
  • Xanthou G, Polihronis M, Tzioufas AG, et al. “Lymphoid” chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of Sjögren’s syndrome patients: possible participation in lymphoid structure formation. Arthritis Rheum. 2001;44:408–418.
  • Kawakami A, Nakashima K, Tamai M, et al. Toll-like receptor in salivary glands from patients with Sjögren’s syndrome: functional analysis by human salivary gland cell line. J Rheumatol. 2007;34:1019–1026.
  • Wang X, Shaalan A, Liefers S, et al. Dysregulation of NF-kB in glandular epithelial cells results in Sjögren’s-like features. Appel S, editor. PLoS One. 2018;13:e0200212.
  • Spachidou MP, Bourazopoulou E, Maratheftis CI, et al. Expression of functional toll-like receptors by salivary gland epithelial cells: increased mRNA expression in cells derived from patients with primary Sjögren’s syndrome. Clin Exp Immunol. 2007;147:497–503.
  • Rusakiewicz S, Nocturne G, Lazure T, et al. NCR3/NKp30 contributes to pathogenesis in primary Sjogren’s syndrome. Sci Transl Med. 2013;5:195ra96.
  • Amft N, Curnow SJ, Scheel-Toellner D, et al. Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren’s syndrome. Arthritis Rheum. 2001;44:2633–2641.
  • Manoussakis MN, Spachidou MP, Maratheftis CI. Salivary epithelial cells from Sjogren’s syndrome patients are highly sensitive to anoikis induced by TLR-3 ligation. J Autoimmun. 2010;35:212–218.
  • Salomonsson S, Jonsson MV, Skarstein K, et al. Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren’s syndrome. Arthritis Rheum. 2003;48:3187–3201.
  • Fox RI, Kang HI, Ando D, et al. Cytokine mRNA expression in salivary gland biopsies of Sjögren’s syndrome. J Immunol. 1994;152:5532–5539.
  • Delli K, Haacke EA, Kroese FGM, et al. Towards personalised treatment in primary Sjögren’s syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis. 2016;75:1933–1938.
  • NIH National Library of medicine. ClinicalTrials.gov [Internet]. 2019.
  • Lee S-J, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol. 2011;7:718–729.
  • Kuznik A, Bencina M, Svajger U, et al. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol. 2011;186:4794–4804.
  • Takeda K, Akira S. Toll-like receptors. Curr Protoc Immunol. 2015;109:1–10.
  • Hemmi H, Akira S. TLR signalling and the function of dendritic cells. Chem Immunol Allergy 2005;86:120-135.
  • Karlsen M, Jakobsen K, Jonsson R, et al. Expression of toll-like receptors in peripheral blood mononuclear cells of patients with primary Sjögren’s syndrome. Scand J Immunol. 2017;85:220–226.
  • Dawson LJ, Caulfield VL, Stanbury JB, et al. Hydroxychloroquine therapy in patients with primary Sjögren’s syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase. Rheumatology (Oxford). 2005;44:449–455.
  • Capolunghi F, Rosado MM, Cascioli S, et al. Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology. 2010;49:2281–2289.
  • Gottenberg J-E, Ravaud P, Puéchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome. JAMA. 2014;312:249.
  • Zheng L, Zhang Z, Yu C, et al. Expression of toll-like receptors 7, 8, and 9 in primary Sjögren’s syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2010;109:844–850.
  • De S, Zhou H, DeSantis D, et al. Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to signal. Proc Natl Acad Sci U S A. 2015;112:9680–9685.
  • Yamashita M, Chattopadhyay S, Fensterl V, et al. Epidermal growth factor receptor is essential for toll-like receptor 3 signaling. Sci Signal. 2012;5:ra50–ra50.
  • Hsu D, Fukata M, Hernandez YG, et al. Toll-like receptor 4 differentially regulates epidermal growth factor-related growth factors in response to intestinal mucosal injury. Lab Invest. 2010;90:1295–1305.
  • Chen W, Lin J, Cao H, et al. Local and systemic IKKε and NFκB signaling associated with Sjögren’s syndrome immunopathogenesis. J Immunol Res. 2015;2015:1–9.
  • Saraux A, J-O P, Devauchelle-Pensec V. Treatment of primary Sjögren syndrome. Nat Rev Rheumatol. 2016;12:456–471.
  • Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome. J Clin Invest. 2002;109:59–68.
  • Nordmark G, Wang C, Vasaitis L, et al. Association of genes in the NF-κB pathway with antibody-positive primary Sjögren’s syndrome. Scand J Immunol. 2013;78:447–454.
  • Ou -T-T, Lin C-H, Lin Y-C, et al. IkBα promoter polymorphisms in patients with primary Sjögren’s syndrome. J Clin Immunol. 2008;28:440–444.
  • Hara M, Abe T, Sugawara S, et al. Long-term safety study of iguratimod in patients with rheumatoid arthritis. 2007;17(1):10-16.
  • Sisto M, Lisi S, Lofrumento DD, et al. Salivary gland expression level of IκBα regulatory protein in Sjögren’s syndrome. J Mol Histol. 2013;44:447–454.
  • Nakamura H, Kawakami A, Ida H, et al. EGF activates PI3K-Akt and NF-κB via distinct pathways in salivary epithelial cells in Sjögren’s syndrome. Rheumatol Int. 2007;28:127–136.
  • Kwok S-K, Cho M-L, Her Y-M, et al. TLR2 ligation induces the production of IL-23/IL-17 via IL-6, STAT3 and NF-kB pathway in patients with primary Sjogren’s syndrome. Arthritis Res Ther. 2012;14:R64.
  • Sisto M, Lorusso L, Lisi S. TLR2 signals via NF-κB to drive IL-15 production in salivary gland epithelial cells derived from patients with primary Sjögren’s syndrome. Clin Exp Med. 2016;17(3):1–10.
  • Lisi S, Sisto M, Lofrumento DD, et al. Sjögren’s syndrome autoantibodies provoke changes in gene expression profiles of inflammatory cytokines triggering a pathway involving TACE/NF-κB. Lab Invest. 2012;92:615–624.
  • Wei L, Xiong H, Li W, et al. Upregulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF-κB pathways. J Oral Pathol Med. 2018;47:847–855.
  • Lilienbaum A, Israël A. From calcium to NF-kappa B signaling pathways in neurons. Mol Cell Biol. 2003;23:2680–2698.
  • Tamiya T, Kashiwagi I, Takahashi R, et al. Suppressors of cytokine signaling (SOCS) proteins and JAK/STAT pathways. Arterioscler Thromb Vasc Biol. 2011;31:980–985.
  • Vartoukian SR, Tilakaratne WM, Seoudi N, et al. Dysregulation of the suppressor of cytokine signalling 3-signal transducer and activator of transcription-3 pathway in the aetiopathogenesis of Sjögren’s syndrome. Clin Exp Immunol. 2014;177:618–629.
  • Lee J, Lee J, Kwok S, et al. JAK ‐1 inhibition suppresses interferon‐induced BAFF production in human salivary gland. Arthritis Rheumatol. 2018;70:2057–2066.
  • Lee J, Lee J, Baek S-Y, et al. THU0264 A selective JAK1 inhibitor, filgotinib suppresses lymphocytic infiltration in salivary gland of non obese diabetic mice via suppression of baff production of salivary gland epithelial cells. Ann Rheum Dis. 2016;75:283.2–283.
  • Maimets M, Rocchi C, Bron R, et al. Long-term in vitro expansion of salivary gland stem cells driven by Wnt signals. Stem Cell Reports. 2016;6:150–162.
  • Knox SM, Lombaert IMA, Haddox CL, et al. Parasympathetic stimulation improves epithelial organ regeneration. Nat Comm. 2013;4:1494.
  • David M, Wong L, Flavell R, et al. STAT activation by epidermal growth factor (EGF) and amphiregulin. Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1. J Biol Chem. 1996;271:9185–9188.
  • Okuma A, Hoshino K, Ohba T, et al. Enhanced apoptosis by disruption of the STAT3-IκB-ζ signaling pathway in epithelial cells induces Sjögren’s syndrome-like autoimmune disease. Immunity. 2013;38:450–460.
  • Abdelhamed S, Ogura K, Yokoyama S, et al. AKT-STAT3 pathway as a downstream target of EGFR signaling to regulate PD-L1 expression on NSCLC cells. J Cancer. 2016;7:1579–1586.
  • Hall BE, Zheng C, Swaim WD, et al. Conditional overexpression of TGF-β1 disrupts mouse salivary gland development and function. Lab Invest. 2010;90:543–555.
  • Moustakas A, Pardali K, Gaal A, et al. Mechanisms of TGF-β signaling in regulation of cell growth and differentiation. Immunol Lett. 2002;82:85–91.
  • Fragoso MA, Patel AK, Nakamura REI, et al. The Wnt/β-catenin pathway cross-talks with STAT3 signaling to regulate survival of retinal pigment epithelium cells. Gottardi C, editor. PLoS One. 2012;7:e46892.
  • Kawada M, Seno H, Uenoyama Y, et al. Signal transducers and activators of transcription 3 activation is involved in nuclear accumulation of beta-catenin in colorectal cancer. Cancer Res. 2006;66:2913–2917.
  • Yan S, Zhou C, Zhang W, et al. β-Catenin/TCF pathway upregulates STAT3 expression in human esophageal squamous cell carcinoma. Cancer Lett. 2008;271:85–97.
  • Cordero JB, Stefanatos RK, Myant K, et al. Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1-driven intestinal stem cell hyperplasia in the drosophila adult midgut. Development. 2012;139:4524–4535.
  • Yu Y, Gu S, Li W, et al. Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-β signaling. Proc Natl Acad Sci U S A. 2017;114:10113–10118.
  • Abu-Helu RF, Dimitriou ID, Kapsogeorgou EK, et al. Induction of salivary gland epithelial cell injury in Sjogren’s syndrome: in vitro assessment of T cell-derived cytokines and fas protein expression. J Autoimmun. 2001;17:141–153.
  • Ping L, Ogawa N, Sugai S. Novel role of CD40 in Fas-dependent apoptosis of cultured salivary epithelial cells from patients with Sjögren’s syndrome. Arthritis Rheum. 2005;52:573–581.
  • Gump JM, Thorburn A. Autophagy and apoptosis: what is the connection? Trends Cell Biol. 2011;21:387–392.
  • Terunuma A, Limgala RP, Park CJ, et al. Efficient procurement of epithelial stem cells from human tissue specimens using a Rho-associated protein kinase inhibitor Y-27632. Tissue Eng Part A. 2010;16:1363–1368.
  • Kong L, Ogawa N, McGuff HS, et al. Bcl-2 family expression in salivary glands from patients with primary Sjögren’s syndrome: involvement of Bax in salivary gland destruction. Clin Immunol Immunopathol. 1998;88:133–141.
  • Jackson NM, Ceresa BP. EGFR-mediated apoptosis via STAT3. Exp Cell Res. 2017;356:93–103.
  • Zhou X-J ZH. Autophagy in immunity. Autophagy. 2012;8:1286–1299.
  • Delgado MA, Deretic V. Toll-like receptors in control of immunological autophagy. Cell Death Differ. 2009;16:976–983.
  • Delgado MA, Elmaoued RA, Davis AS, et al. Toll-like receptors control autophagy. Embo J. 2008;27:1110–1121.
  • Into T, Inomata M, Takayama E, et al. Autophagy in regulation of Toll-like receptor signaling. Cell Signal. 2012;24:1150–1162.
  • Silver N, Proctor GB, Arno M, et al. Activation of mTOR coincides with autophagy during ligation-induced atrophy in the rat submandibular gland. Cell Death Dis. 2010;1:e14–e14.
  • Fu J, Shi H, Cao N, et al. Toll-like receptor 9 signaling promotes autophagy and apoptosis via divergent functions of the p38/JNK pathway in human salivary gland cells. Exp Cell Res. 2019;375:51-59.
  • Nayar S, Campos J, Smith CG, et al. Phosphatidylinositol 3-kinase delta pathway: a novel therapeutic target for Sjögren’s syndrome. Ann Rheum Dis. 2019;78:249–260.
  • Schwartz M. Rho signalling at a glance. J Cell Sci. 2004;117:5457–5458.
  • Sun -C-C, Chiu H-T, Lin Y-F, et al. Y-27632, a ROCK inhibitor, promoted limbal epithelial cell proliferation and corneal wound healing. Liu X, editor. PLoS One. 2015;10:e0144571.
  • Daley WP, Gulfo KM, Sequeira SJ, et al. Identification of a mechanochemical checkpoint and negative feedback loop regulating branching morphogenesis. Dev Biol. 2009;336:169–182.
  • Crema VO, Hamassaki DE, Santos MF. Small Rho GTPases are important for acinus formation in a human salivary gland cell line. Cell Tissue Res. 2006;325:493–500.
  • Gervais EM, Sequeira SJ, Wang W, et al. Par-1b is required for morphogenesis and differentiation of myoepithelial cells during salivary gland development. Organogenesis. 2016;12:194–216.
  • Li J, Cong X, Zhang Y, et al. ZO-1 and −2 are required for TRPV1-modulated paracellular permeability. J Dent Res. 2015;94:1748–1756.
  • Lee J, Park S, Roh S. Y-27632, a ROCK inhibitor, delays senescence of putative murine salivary gland stem cells in culture. Arch Oral Biol. 2015;60:875–882.
  • Hwang S-M, Jin M, Shin YH, et al. Role of LPA and the hippo pathway on apoptosis in salivary gland epithelial cells. Exp Mol Med. 2014;46:e125–e125.
  • Han C, An GH, Woo D-H, et al. Rho-associated kinase inhibitor enhances the culture condition of isolated mouse salivary gland cells in vitro. Tissue Cell. 2018;54:20–25.