Changes of transporters expression and activity in rheumatoid arthritis

doi:10.12092/j.issn.1009-2501.2018.02.020

Abstract

Abstract:

Inflammatory disease state will release a large number of inflammatory cytokines, and accompanied by drug transporters expression and activity changes. Drug transporters are present in various tissues and have an important role in drug absorption, distribution, and elimination. Expression and activity changes will affect the body's plasma concentration, accumulation, the effectiveness of drug treatment, and even produce multidrug resistance, drug-drug interactions and so on. Rheumatoid arthritis is a common inflammatory disease that releases a large number of inflammatory cytokines, with changes in expression and activity of the transporters, which affects the therapeutic effect and changes the expression and activity of the drug transporters. This review summarizes the knowledge on the roles of transporters in rheumatoid arthritis in order to provide a new direction for the treatment of rheumatoid arthritis.

Key words: rheumatoid arthritis, SLC transporters, ABC transporters

CLC Number:

R392.5

DU Juan, XU Lingyan, WU Wei, SHENG Qingqing, JIANG Zhenzhou, ZHANG Luyong, HUANG Xin. Changes of transporters expression and activity in rheumatoid arthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(2): 223-229.

References

［1］Smolen JS, Aletaha D, Mcinnes IB. Rheumatoid arthritis［J］. Lancet, 2016, 388(10055): 2023.
［2］Okada M, Fujii H, Suga Y, et al. Drug interaction between methotrexate and salazosulfapyridine in Japanese patients with rheumatoid arthritis［J］. J Pharm Health Care Sci, 2017, 3(1): 7.
［3］Lee SW, Kim JH, Park MC, et al. Alleviation of rheumatoid arthritis by cell-transducible methotrexate upon transcutaneous delivery［J］. Biomaterials, 2012, 33(5): 1563-1572.
［4］Pavkova GM, Lipkova J, Pavek N, et al. RANTES, MCP-1 chemokines and factors describing rheumatoid arthritis［J］. Mol Immunol, 2012, 52(3-4): 273-278.
［5］Kokkonen H, Sderstrm I, Rocklv J, et al. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis［J］. Arthritis & Rheum, 2010, 62(2): 383-391.
［6］Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics［J］. Clin Pharmacol Ther, 2009, 85(4): 434-438.
［7］Markova S, Nakamura T, Sakaeda T, et al. Genotype-dependent down-regulation of gene expression and function of MDR1 in human peripheral blood mononuclear cells under acute inflammation［J］. Drug Metab Pharmacokinet, 2006, 21(3): 194-200.
［8］Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution［J］. Eur J Pharm Sci, 2006, 27(5): 425-446.
［9］Morris ME, Rodriguez-Cruz V, Felmlee MA. SLC and ABC transporters: expression, localization, and species differences at the blood-brain and the blood-cerebrospinal fluid barriers［J］. AAPS J, 2017, 19(5):1317-1331
［10］Koepsell H, Endou H. The SLC22 drug transporter family［J］. Pflügers Archiv - European Journal of Physiology, 2004, 447(5): 666-676.
［11］李聃, 盛莉, 李燕. 药物转运体的研究方法［J］. 药学学报, 2014, 49(7): 963-970.
［12］马莉, 饶志, 武新安. 药物转运体在药物排泄中的作用［J］. 中国药学杂志, 2013, 48(8): 582-586.
［13］Mizuno N, Niwa T, Yotsumoto Y, et al. Impact of drug transporter studies on drug discovery and development［J］. Pharmacol Rev, 2003, 55(3): 425-461.
［14］Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications［J］. Pharm Res, 2007, 24(7): 1227-1251.
［15］Sai Y. Biochemical and molecular pharmacological aspects of transporters as determinants of drug disposition［J］. Drug Metab Pharmacokinet, 2005, 20(2): 91-99.
［16］Tyden E, Bjornstrom H, Tjalve H, et al. Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse［J］. J Vet Pharmacol Ther, 2010, 33(4): 332-340.
［17］Grube M, Kck K, Karner S, et al. Modification of OATP2B1-mediated transport by steroid hormones［J］. Molecular Pharmacology, 2006, 70(5): 1735-1741.
［18］Ronaldson PT, Ashraf T, Bendayan R. Regulation of multidrug resistance protein 1 by tumor necrosis factor alpha in cultured glial cells: involvement of nuclear factor-kappaB and c-Jun N-terminal kinase signaling pathways［J］. Mol Pharmacol, 2010, 77(4): 644-659.
［19］Qiang F, Lee B J, Lee W, et al. Pharmacokinetic drug interaction between fexofenadine and fluvastatin mediated by organic anion-transporting polypeptides in rats［J］. Eur J Pharm Sci, 2009, 37(3-4): 413-417.
［20］Morgan ET, Lee CM, Nyagode BA. Regulation of drug metabolizing enzymes and transporters in infection, inflammation, and cancer［M］. John Wiley & Sons, Inc., 2008: 123-149.
［21］Harvey RD, Morgan ET. Cancer, inflammation, and therapy: effects on cytochrome p450-mediated drug metabolism and implications for novel immunotherapeutic agents［J］. Clin Pharmacol Ther, 2014, 96(4): 449-457.
［22］Le Vee M, Jouan E, Stieger B, et al. Regulation of drug transporter expression by oncostatin M in human hepatocytes［J］. Biochem Pharmacol, 2011, 82(3): 304-311.
［23］Geier A, Wagner M, Dietrich CG, et al. Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration［J］. Biochim Biophys Acta, 2007, 1773(3): 283-308.
［24］Tazoe Y, Hayashi H, Tsuboi S, et al. Reduced folate carrier 1 gene expression levels are correlated with methotrexate efficacy in Japanese patients with rheumatoid arthritis［J］. Drug Metab Pharmacokinet, 2015, 30(3): 227-230.
［25］Lin L, Yee SW, Kim RB, et al. SLC transporters as therapeutic targets: emerging opportunities［J］. Nat Rev Drug Discov, 2015, 14(8):543-560.
［26］Feldmann M, Maini SR. Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics［J］. Immunol Rev, 2008, 223: 7-19.
［27］Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution［J］. Eur J Pharm Sci, 2006, 27(5): 425-446.
［28］Fisher CD, Lickteig AJ, Augustine LM, et al. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats［J］. Eur J Pharmcol, 2009, 613(1-3): 119-127.
［29］Renton KW. Cytochrome P450 regulation and drug biotransformation during inflammation and infection［J］. Curr Drug Metab, 2004, 5(3): 235-243.
［30］Maeda T, Hirayama M, Kobayashi D, et al. Mechanism of the regulation of organic cation/carnitine transporter 1 (SLC22A4) by rheumatoid arthritis-associated transcriptional factor RUNX1 and inflammatory cytokines［J］. Drug MetabDispos, 2007, 35(3): 394-401.
［31］Uno S, Uraki M, Ito A, et al. Changes in mRNA expression of ABC and SLC transporters in liver and intestines of the adjuvant-induced arthritis rat［J］. Biopharm Drug Dispos, 2009, 30(1): 49.
［32］Han HK. Role of transporters in drug interactions［J］. Archiv Pharmacal Res, 2011, 34(11): 501-517.
［33］Momper JD, Tsunoda SM, Ma JD. Evaluation of proposed in vivo probe substrates and inhibitors for phenotyping transporter activity in humans［J］. J Clin Pharmacol, 2016, 56 Suppl 7(S7): S82-98.
［34］Murakami T, Mori N. Involvement of multiple transporters-mediated transports in mizoribine and methotrexate pharmacokinetics［J］. Pharmaceuticals (Basel), 2012, 5(8): 802-836.
［35］Feng Y, Wang C, Liu Q, et al. Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats［J］. Eur J Pharm Sci, 2016, 81: 119-128.
［36］Ren TL, Han ZJ, Yang CJ, et al. Association of SLC22A4 gene polymorphism with rheumatoid arthritis in the Chinese population［J］. J Biochem Mol Toxicol, 2014, 28(5): 206-210.
［37］Lima A, Bernardes M, Azevedo R, et al. SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients［J］. Toxicol Sci, 2014, 142(1): 196-209.
［38］Hediger MA, Clémenon B, Burrier RE, et al. The ABCs of membrane transporters in health and disease (SLC series): Introduction［J］. Mol Aspects Med, 2013, 34(2-3): 95-107.
［39］Neumann J, Rose-Sperling D, Hellmich UA. Diverse relations between ABC transporters and lipids: An overview［J］. Biochim Biophys Acta, 2017, 1859(4): 605-618.
［40］Doerks T, Copley RR, Schultz J, et al. Systematic identification of novel protein domain families associated with nuclear functions［J］. Genome Res, 2002, 12(1): 47-56.
［41］ Kawase A, Norikane S, Okada A, et al. Distinct alterations in ATP-Binding cassette transporter expression in liver, kidney, small intestine, and brain in adjuvant-induced arthritic rats［J］. J Pharm Sci, 2014, 103(8): 2556-2264.
［42］Kawase A, Yoshida I, Tsunokuni Y, et al. Decreased PXR and CAR inhibit transporter and CYP mRNA Levels in the liver and intestine of mice with collagen-induced arthritis［J］. Xenobiotica, 2007, 37(4): 366-374.
［43］Uno S, Kawase A, Tsuji A, et al. Decreased intestinal CYP3A and P-glycoprotein activities in rats with adjuvant arthritis［J］. Drug Metab Pharmacokinet, 2007, 22(4): 313-321.
［44］Marquez B, Van BF. ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions［J］. Curr Drug Targets, 2011, 12(5): 600-620.
［45］Tsujimura S, Saito K, Nawata M, et al. Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis［J］. Ann Rheum Dis, 2008, 67(3): 380-388.
［46］Schwarz UI, Meyer zu Schwabedissen HE, Tirona RG, et al. Identification of novel functional organic anion-transporting polypeptide 1B3 polymorphisms and assessment of substrate specificity［J］. Pharmacogenet Genomics, 2011, 21(3): 103-114.
［47］García-Carrasco M, Mendoza-Pinto C, Macias DS, et al. P-glycoprotein in autoimmune rheumatic diseases［J］. Autoimmun Rev, 2015, 14(7): 594-600.
［48］Lima A, Bernardes M, Azevedo R, et al. Pharmacogenomics of methotrexate membrane transport pathway: can clinical response to methotrexate in rheumatoid arthritis be predicted［J］? Int J Mol Sci, 2015, 16(6): 13760-13780.
［49］Mazerska Z, Mroz A, Pawlowska M, et al. The role of glucuronidation in drug resistance［J］. Pharmacol Ther, 2016, 159: 35-55.
［50］Agarwal V, Mittal SK, Misra R. Expression of multidrug resistance-1 protein correlates with disease activity rather than the refractoriness to methotrexate therapy in rheumatoid arthritis［J］. Clin Rheumatol, 2009, 28(4): 427-433.
［51］Rodriguez JM, Monsalves-Alvarez M, Henriquez S, et al. Glucocorticoid resistance in chronic diseases［J］. Steroids, 2016, 115: 182-192.
［52］Liu YM, Chen JW, Chen LX, et al. Overexpression of P-glycoprotein on fibroblast-like synoviocytes in refractory rheumatoid arthritis patients: a potential mechanism for multidrug resistance in rheumatoid arthritis treatment［J］. Genet Mol Res, 2016, 15(2).
［53］Marki-Zay J, Tauberne Jakab K, Szeremy P, et al. MDR-ABC transporters: biomarkers in rheumatoid arthritis［J］. Clin Exp Rheumatol, 2013, 31(5): 779-787.
［54］Chen QX, Hu HH, Zhou Q, et al. An overview of ABC and SLC drug transporter gene regulation［J］. Curr Drug Metab, 2013, 14(2): 253-264.
［55］Sissung TM, Troutman SM, Campbell TJ, et al. Transporter pharmacogenetics: transporter polymorphisms affect normal physiology, diseases, and pharmacotherapy［J］. Discov Med, 2012, 13(68): 19-34.

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