Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation

References

• Ahmad SF, Ansari MA, Nadeem A, Zoheir KMA, Bakheet SA, Alsaad AMS, Al-Shabanah OA, Attia SM. 2017. STA-21, a STAT-3 inhibitor, attenuates the development and progression of inflammation in collagen antibody-induced arthritis. Immunobiology. 222(2):206–217.
   PubMed Web of Science ®Google Scholar
• Alhazzani K, Ahmad SF, Al-Harbi NO, Attia SM, Bakheet SA, Sarawi W, Alqarni SA, Algahtani M, Nadeem A. 2021. Pharmacological inhibition of STAT3 by static ameliorates clinical symptoms and reduces autoinflammation in myeloid, lymphoid, and neuronal tissue compartments in relapsing-remitting model of experimental autoimmune encephalomyelitis in SJL/J mice. Pharmaceutics. 13(7):925–938.
   PubMed Web of Science ®Google Scholar
• Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, et al. 2012. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 8(10):839–847.
   PubMed Web of Science ®Google Scholar
• Angiari S, Runtsch MC, Sutton CE, Palsson-McDermott EM, Kelly B, Rana N, Kane H, Papadopoulou G, Pearce EL, Mills KHG, et al. 2020. Pharmacological activation of pyruvate kinase M2 inhibits CD4+ T cell pathogenicity and suppresses autoimmunity. Cell Metab. 31(2):391.e8–405.e8.
   Web of Science ®Google Scholar
• Blanco FJ, Moricke R, Dokoupilova E, Codding C, Neal J, Andersson M, Rohrer S, Richards H. 2017. Secukinumab in active rheumatoid arthritis: a phase III randomized, double-blind, active comparator- and placebo-controlled study. Arthritis Rheumatol. 69(6):1144–1153.
   PubMed Web of Science ®Google Scholar
• Buck MD, O'Sullivan D, Pearce EL. 2015. T cell metabolism drives immunity. J Exp Med. 212(9):1345–1360.
   PubMed Web of Science ®Google Scholar
• Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O'Shea JJ. 2006. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA. 103(21):8137–8142.
   PubMed Web of Science ®Google Scholar
• Damasceno LEA, Prado DS, Veras FP, Fonseca MM, Toller-Kawahisa JE, Rosa MH, Publio GA, Martins TV, Ramalho FS, Waisman A, et al. 2020. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. J Exp Med. 217:e20190613.
   PubMed Web of Science ®Google Scholar
• Dong G, Mao Q, Xia W, Xu Y, Wang J, Xu L, Jiang F. 2016. PKM2 and cancer: the function of PKM2 beyond glycolysis. Oncol Lett. 11(3):1980–1986.
   PubMed Web of Science ®Google Scholar
• Fragoulis GE, Siebert S, McInnes IB. 2016. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med. 67:337–353.
   PubMed Web of Science ®Google Scholar
• Freitag J, Berod L, Kamradt T, Sparwasser T. 2016. Immunometabolism and autoimmunity. Immunol Cell Biol. 94(10):925–934.
   PubMed Web of Science ®Google Scholar
• Hou PP, Luo LJ, Chen HZ, Chen QT, Bian XL, Wu SF, Zhou JX, Zhao WX, Liu JM, Wang XM, et al. 2020. Ectosomal PKM2 promotes HCC by inducing macrophage differentiation and remodeling the tumor microenvironment. Mol Cell. 78(6):1192.e10–1206.e10.
   Web of Science ®Google Scholar
• Israelsen WJ, Vander Heiden MG. 2015. Pyruvate kinase: function, regulation and role in cancer. Semin Cell Dev Biol. 43:43–51.
   PubMed Web of Science ®Google Scholar
• Jang YJ, Kim ME, Ko SY. 2011. n-Butanol extracts of Panax notoginseng suppress LPS-induced MMP-2 expression in periodontal ligament fibroblasts and inhibit osteoclastogenesis by suppressing MAPK in LPS-activated RAW264.7 cells. Arch Oral Biol. 56(11):1319–1327.
   PubMed Web of Science ®Google Scholar
• Jiang X, Wang S, Zhou C, Wu J, Jiao Y, Lin L, Lu X, Yang B, Zhang W, Xiao X, et al. 2020. Comprehensive TCR repertoire analysis of CD4+ T-cell subsets in rheumatoid arthritis. J Autoimmun. 109:102432.
   PubMed Web of Science ®Google Scholar
• Keller KE, Tan IS, Lee YS. 2012. SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science. 338(6110):1069–1072.
   PubMed Web of Science ®Google Scholar
• Komatsu N, Okamoto K, Sawa S, Nakashima T, Oh-Hora M, Kodama T, Tanaka S, Bluestone JA, Takayanagi H. 2014. Pathogenic conversion of Foxp3+ T cells into Th17 cells in autoimmune arthritis. Nat Med. 20(1):62–68.
   PubMed Web of Science ®Google Scholar
• Komuczki J, Tuzlak S, Friebel E, Hartwig T, Spath S, Rosenstiel P, Waisman A, Opitz L, Oukka M, Schreiner B, et al. 2019. Fate-mapping of GM-CSF expression identifies a discrete subset of inflammation-driving T helper cells regulated by cytokines IL-23 and IL-1beta. Immunity. 50(5):1289–1304 e1286.
   PubMed Web of Science ®Google Scholar
• Kono M, Maeda K, Stocton-Gavanescu I, Pan WL, Umeda M, Katsuyama E, Burbano C, Orite SYK, Vukelic M, Tsokos MG, et al. 2019. Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation. JCI Insight. 4(12):e127395.
   PubMed Web of Science ®Google Scholar
• Korn T, Bettelli E, Oukka M, Kuchroo VK. 2009. IL-17 and Th17 Cells. Annu Rev Immunol. 27:485–517.
   PubMed Web of Science ®Google Scholar
• Li XD, Chang B, Chen B, Liu ZY, Liu DX, Wang JS, Hou GQ, Huang DY, Du SX. 2010. Panax notoginseng saponins potentiate osteogenesis of bone marrow stromal cells by modulating gap junction intercellular communication activities. Cell Physiol Biochem. 26(6):1081–1092.
   PubMedGoogle Scholar
• Li XY. 1991. Immunomodulating Chinese herbal medicines. Mem Inst Oswaldo Cruz. 86(Suppl 2):159–164.
   PubMedGoogle Scholar
• Ma R, Liu Q, Zheng S, Liu T, Tan D, Lu X. 2019. PKM2-regulated STAT3 promotes esophageal squamous cell carcinoma progression via TGF-beta1-induced EMT. J Cell Biochem. 120(7):11539–11550.
   PubMed Web of Science ®Google Scholar
• McInnes IB, Schett G. 2011. The pathogenesis of rheumatoid arthritis. N Engl J Med. 365(23):2205–2219.
   PubMed Web of Science ®Google Scholar
• Nadeem A, Ahmad SF, Al-Harbi NO, Siddiqui N, Ibrahim KE, Attia SM. 2018. Inhibition of BET bromodomains restores corticosteroid responsiveness in a mixed granulocytic mouse model of asthma. Biochem Pharmacol. 154:222–233.
   PubMed Web of Science ®Google Scholar
• Okano T, Saegusa J, Takahashi S, Ueda Y, Morinobu A. 2018. Immunometabolism in rheumatoid arthritis. Immunol Med. 41(3):89–97.
   PubMedGoogle Scholar
• Prakasam G, Iqbal MA, Bamezai RNK, Mazurek S. 2018. Posttranslational modifications of pyruvate kinase M2: tweaks that benefit cancer. Front Oncol. 8:22.
   PubMed Web of Science ®Google Scholar
• Raez LE, Papadopoulos K, Ricart AD, Chiorean EG, Dipaola RS, Stein MN, Rocha Lima CM, Schlesselman JJ, Tolba K, Langmuir VK, et al. 2013. A phase I dose-escalation trial of 2-deoxy-d-glucose alone or combined with docetaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 71(2):523–530.
   PubMed Web of Science ®Google Scholar
• Seki SM, Posyniak K, McCloud R, Rosen DA, Fernandez-Castaneda A, Beiter RM, Serbulea V, Nanziri SC, Hayes N, Spivey C, et al. 2020. Modulation of PKM activity affects the differentiation of Th17 cells. Sci Signal. 13:eaay9217.
   PubMed Web of Science ®Google Scholar
• Shen Y, Wen Z, Li Y, Matteson EL, Hong J, Goronzy JJ, Weyand CM. 2017. Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells. Nat Immunol. 18(9):1025–1034.
   PubMed Web of Science ®Google Scholar
• Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H. 2011. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of Th17 and Treg cells. J Exp Med. 208(7):1367–1376.
   PubMed Web of Science ®Google Scholar
• Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, et al. 2018. Rheumatoid arthritis. Nat Rev Dis Primers. 4:18001.
   PubMed Web of Science ®Google Scholar
• Srivastava RK, Dar HY, Mishra PK. 2018. Immunoporosis: immunology of osteoporosis-role of T cells. Front Immunol. 9:657.
   PubMed Web of Science ®Google Scholar
• Uzayisenga R, Ayeka PA, Wang Y. 2014. Anti-diabetic potential of Panax notoginseng saponins (PNS): a review. Phytother Res. 28(4):510–516.
   PubMed Web of Science ®Google Scholar
• van Hamburg JP, Tas SW. 2018. Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis. J Autoimmun. 87:69–81.
   PubMed Web of Science ®Google Scholar
• Wang T, Guo R, Zhou G, Zhou X, Kou Z, Sui F, Li C, Tang L, Wang Z. 2016. Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: a review. J Ethnopharmacol. 188:234–258.
   PubMed Web of Science ®Google Scholar
• Wei CC, Yue LF, You FT, Tao C. 2021. Panax notoginseng saponins alleviate osteoporosis and joint destruction in rabbits with antigen-induced arthritis. Exp Ther Med. 22(5):1302.
   PubMed Web of Science ®Google Scholar
• Wei JR, Wen X, Bible PW, Li Z, Nussenblatt RB, Wei L. 2017. Panax notoginseng saponin controls IL-17 expression in helper T cells. J Ocul Pharmacol Ther. 33(4):285–289.
   PubMed Web of Science ®Google Scholar
• Weyand CM, Goronzy JJ. 2020. Immunometabolism in the development of rheumatoid arthritis. Immunol Rev. 294(1):177–187.
   PubMed Web of Science ®Google Scholar
• Wu L, Hollinshead KER, Hao Y, Au C, Kroehling L, Ng C, Lin WY, Li D, Silva HM, Shin J, et al. 2020. Niche-selective inhibition of pathogenic Th17 cells by targeting metabolic redundancy. Cell. 182(3):641.e20–654.e20.
   Web of Science ®Google Scholar
• Yang J, Sundrud MS, Skepner J, Yamagata T. 2014. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci. 35(10):493–500.
   PubMed Web of Science ®Google Scholar
• Yang P, Qian FY, Zhang MF, Xu AL, Wang X, Jiang BP, Zhou LL. 2019. Th17 cell pathogenicity and plasticity in rheumatoid arthritis. J Leukoc Biol. 106(6):1233–1240.
   PubMed Web of Science ®Google Scholar
• Yang P, Zhang M, Wang X, Xu AL, Shen M, Jiang B, Zhou X, Zhou L. 2020. MicroRNA let-7g-5p alleviates murine collagen-induced arthritis by inhibiting Th17 cell differentiation. Biochem Pharmacol. 174:113822.
   PubMed Web of Science ®Google Scholar