Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Chemokines: A Potential Therapeutic Target to Suppress Autoimmune Arthritis

Author(s): Mahmood A. Khan, Nikhil Khurana, Rafat S. Ahmed, Sadiq Umar, Abu H. Md. G. Sarwar, Qamre Alam, Mohammad A. Kamal and Ghulam Md Ashraf*

Volume 25 , Issue 27 , 2019

Page: [2937 - 2946] Pages: 10

DOI: 10.2174/1381612825666190709205028

Price: $65


Background: Chemokines are a family of low molecular weight proteins that induce chemotaxis of inflammatory cells, which mainly depends on the recognition of a chemo-attractant gradient and interaction with the substratum. In Rheumatoid Arthritis (RA), abundant chemokines are expressed in synovial tissue, cause inflammatory cells migration into the inflamed joint that necessitates the formation of new blood vessels i.e. angiogenesis. Over the decades, studies showed that continuous inflammation may lead to the loss of tissue architecture and function, causing severe disability and cartilage destruction. In spite of the advancement of modern drug therapy, thousands of arthritic patients suffer mortality and morbidity globally. Thus, there is an urgent need for the development of novel therapeutic agents for the treatment of RA.

Methods: This review is carried out throughout a non-systematic search of the accessible literature, will provide an overview of the current information of chemokine in RA and also exploring the future perspective of the vital role of targeting chemokine in RA treatment.

Results: Since, chemokines are associated with inflammatory cells/leucocyte migration at the site of inflammation in chronic inflammatory diseases and hence, blockade or interference with chemokines activity showing a potential approach for the development of new anti-inflammatory agents. Currently, results obtained from both preclinical and clinical studies showed significant improvement in arthritis.

Conclusion: This review summarizes the role of chemokines and their receptors in the pathogenesis of RA and also indicates possible interactions of chemokines/receptors with various synthetic and natural compounds that may be used as a potential therapeutic target in the future for the treatment of RA.

Keywords: Rheumatiod arthritis, chemokines, cytokines, inflammation, synovial tissue, cartilage destruction.

Takemura S, Braun A, Crowson C, et al. Lymphoid neogenesis in rheumatoid synovitis. J Immunol 2001; 167(2): 1072-80.
[] [PMID: 11441118]
Cyster JG. Chemokines and cell migration in secondary lymphoid organs. Science 1999; 286(5447): 2098-102.
[] [PMID: 10617422]
Koch AE, Kunkel SL, Harlow LA, et al. Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis. J Clin Invest 1994; 93(3): 921-8.
[] [PMID: 8132778]
Haq SK, Rabbani G, Ahmad E, Atif SM, Khan RH. Protease inhibitors: A panacea? J Biochem Mol Toxicol 2010; 24(4): 270-7.
[] [PMID: 20135636]
D’Ambrosio D, Panina-Bordignon P, Sinigaglia F. Chemokine receptors in inflammation: An overview. J Immunol Methods 2003; 273(1-2): 3-13.
[] [PMID: 12535793]
Alexander SP, Mathie A, Peters JA. Guide to receptors and channels (GRAC) fifth Ed Br J Pharmacol. 2011; 164:: pp. S1-324.
Zhebrun DA, Totolyan AA, Maslyanskii AL, et al. Synthesis of some CC chemokines and their receptors in the synovium in rheumatoid arthritis. Bull Exp Biol Med 2014; 158(2): 192-6.
[] [PMID: 25430645]
Rossato C, Albuquerque LL, Katz ISS, et al. Early Peritoneal CC Chemokine Production Correlates with Divergent Inflammatory Phenotypes and Susceptibility to Experimental Arthritis in Mice. J Immunol Res 2019; 20192641098
[] [PMID: 30937315]
Yamaguchi A, Nozawa K, Fujishiro M, et al. CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis. Mod Rheumatol 2013; 23(5): 856-63.
[] [PMID: 23007802]
Gao F, Tian J, Pan H, Gao J, Yao M. Association of CCL13 levels in serum and synovial fluid with the radiographic severity of knee osteoarthritis. J Investig Med 2015; 63(3): 545-7.
[] [PMID: 25654294]
Bugatti S, Manzo A, Vitolo B, et al. High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease. Rheumatology (Oxford) 2014; 53(10): 1886-95.
[] [PMID: 24764267]
Greisen SR, Schelde KK, Rasmussen TK, et al. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’. Arthritis Res Ther 2014; 16(5): 434.
[] [PMID: 25249397]
Shi LJ, Li JH, Hu FL, et al. Clinical significance of serum C-C chemokine ligand 19 levels in patients with rheumatoid arthritis. Beijing Da Xue Xue Bao 2016; 48: 667-71.
Pathak JL, Bakker AD, Verschueren P, et al. CXCL8 and CCL20 Enhance osteoclastogenesis via modulation of cytokine production by human primary osteoblasts. PLoS One 2015; 10(6)e0131041
[] [PMID: 26103626]
Kuo SJ, Huang CC, Tsai CH, Hsu HC, Su CM, Tang CH. Chemokine C-C Motif Ligand 4 Gene Polymorphisms Associated with Susceptibility to Rheumatoid Arthritis. BioMed Res Int 2018; 20189181647
[] [PMID: 29955612]
Yeo L, Adlard N, Biehl M, et al. Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis. Ann Rheum Dis 2016; 75(4): 763-71.
[] [PMID: 25858640]
Halloran MM, Woods JM, Strieter RM, et al. The role of an epithelial neutrophil-activating peptide-78-like protein in rat adjuvant-induced arthritis. J Immunol 1999; 162(12): 7492-500.
[PMID: 10358204]
Lee EY, Lee ZH, Song YW. The interaction between CXCL10 and cytokines in chronic inflammatory arthritis. Autoimmun Rev 2013; 12(5): 554-7.
[] [PMID: 23092582]
Antonelli A, Ferrari SM, Giuggioli D, Ferrannini E, Ferri C, Fallahi P. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmun Rev 2014; 13(3): 272-80.
[] [PMID: 24189283]
Kotrych D, Dziedziejko V, Safranow K, Drozdzik M, Pawlik A. CXCL9 and CXCL10 gene polymorphisms in patients with rheumatoid arthritis. Rheumatol Int 2015; 35(8): 1319-23.
[] [PMID: 25702175]
Ibrahim I, Humphreys J, Mokhtar I, et al. Association of chemokine CXC ligand 12 gene polymorphism (rs1746048) with cardiovascular mortality in patients with rheumatoid arthritis: results from the Norfolk Arthritis Register. Ann Rheum Dis 2015; 74(11): 2099-102.
[] [PMID: 26324845]
Gao B, Lin J, Jiang Z, et al. Upregulation of chemokine CXCL10 enhances chronic pulmonary inflammation in tree shrew collagen-induced arthritis. Sci Rep 2018; 8(1): 9993.
[] [PMID: 29968810]
Cecchinato V, D’Agostino G, Raeli L, et al. Redox-mediated mechanisms fuel monocyte responses to CXCL12/HMGB1 in active rheumatoid arthritis. Front Immunol 2018; 9: 2118.
[] [PMID: 30283452]
Jones JD, Hamilton BJ, Challener GJ, et al. Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels. Arthritis Res Ther 2014; 16(2): R103.
[] [PMID: 24766912]
Li CH, Xu LL, Zhao JX, et al. CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway. Inflamm Res 2016; 65(3): 193-202.
[] [PMID: 26621504]
Nanki T, Imai T, Kawai S. Fractalkine/CX3CL1 in rheumatoid arthritis. Mod Rheumatol 2017; 27(3): 392-7.
[] [PMID: 27484962]
Blaschke S, Müller GA. [Fractalkine--a proinflammatory chemokine in rheumatoid arthritis]. Z Rheumatol 2008; 67(5): 424-8.
[PMID: 18633630]
Haringman JJ, Smeets TJ, Reinders-Blankert P, Tak PP. Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann Rheum Dis 2006; 65(3): 294-300.
[] [PMID: 16107514]
Wang B, Zinselmeyer BH, Runnels HA, et al. In vivo imaging implicates CCR2(+) monocytes as regulators of neutrophil recruitment during arthritis. Cell Immunol 2012; 278(1-2): 103-12.
[] [PMID: 23121982]
Li N, Wei W, Yin F, et al. The abnormal expression of CCR4 and CCR6 on Tregs in rheumatoid arthritis. Int J Clin Exp Med 2015; 8(9): 15043-53.
[PMID: 26628988]
Liu X, Zhang H, Chang X, et al. Upregulated expression of CCR3 in rheumatoid arthritis and CCR3-dependent activation of fibroblast-like synoviocytes. Cell Biol Toxicol 2017; 33(1): 15-26.
[] [PMID: 27495116]
Rossol M, Pierer M, Arnold S, et al. Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis. Arthritis Res Ther 2009; 11(3): R91.
[] [PMID: 19538721]
Rodríguez-Rodríguez L, González-Juanatey C, García-Bermúdez M, et al. CCR5Δ32 variant and cardiovascular disease in patients with rheumatoid arthritis: A cohort study. Arthritis Res Ther 2011; 13(4): R133.
[] [PMID: 21846359]
Hinks A, Martin P, Flynn E, et al. Association of the CCR5 gene with juvenile idiopathic arthritis. Genes Immun 2010; 11(7): 584-9.
[] [PMID: 20463745]
Cheng P, Zhang Y, Huang H, et al. Association between CCR6 and rheumatoid arthritis: A meta-analysis. Int J Clin Exp Med 2015; 8(4): 5388-96.
[PMID: 26131115]
Perkins EA, Landis D, Causey ZL, et al. Association of single-nucleotide polymorphisms in CCR6, TAGAP, and TNFAIP3 with rheumatoid arthritis in African Americans. Arthritis Rheum 2012; 64(5): 1355-8.
[] [PMID: 22127930]
Paulissen SM, van Hamburg JP, Davelaar N, et al. CCR6(+) Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis. Arthritis Res Ther 2015; 17: 344.
[] [PMID: 26617177]
Yokoyama W, Kohsaka H, Kaneko K, et al. Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice. Arthritis Res Ther 2014; 16(5): 445.
[] [PMID: 25248373]
Chen Z, Kim SJ, Essani AB, et al. Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis. Ann Rheum Dis 2015; 74(10): 1898-906.
[] [PMID: 24833787]
Aldahlawi AM, Elshal MF, Ashgan FT, Bahlas S. Chemokine receptors expression on peripheral CD4-lymphocytes in rheumatoid arthritis: Coexpression of CCR7 and CD95 is associated with disease activity. Saudi J Biol Sci 2015; 22(4): 453-8.
[] [PMID: 26150752]
Coelho FM, Pinho V, Amaral FA, et al. The chemokine receptors CXCR1/CXCR2 modulate antigen-induced arthritis by regulating adhesion of neutrophils to the synovial microvasculature. Arthritis Rheum 2008; 58(8): 2329-37.
[] [PMID: 18668539]
Bryant J, Ahern DJ, Brennan FM. CXCR4 and vascular cell adhesion molecule 1 are key chemokine/adhesion receptors in the migration of cytokine-activated T cells. Arthritis Rheum 2012; 64(7): 2137-46.
[] [PMID: 22275188]
Laragione T, Brenner M, Sherry B, Gulko PS. CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthritis. Arthritis Rheum 2011; 63(11): 3274-83.
[] [PMID: 21811993]
Slauenwhite D, Gebremeskel S, Doucette CD, Hoskin DW, Johnston B. Regulation of cytokine polarization and T cell recruitment to inflamed paws in mouse collagen-induced arthritis by the chemokine receptor CXCR6. Arthritis Rheumatol 2014; 66(11): 3001-12.
[] [PMID: 25132679]
Matsukawa A, Miyazaki S, Maeda T, et al. Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits: Roles of tumor necrosis factor alpha, interleukin-1, and interleukin-8. Lab Invest 1998; 78(8): 973-85.
[PMID: 9714185]
Shahrara S, Proudfoot AE, Park CC, et al. Inhibition of monocyte chemoattractant protein-1 ameliorates rat adjuvant-induced arthritis. J Immunol 2008; 180(5): 3447-56.
[] [PMID: 18292571]
Borzì RM, Mazzetti I, Cattini L, Uguccioni M, Baggiolini M, Facchini A. Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines. Arthritis Rheum 2000; 43(8): 1734-41.
[<1734:AID-ANR9>3.0.CO;2-B] [PMID: 10943863]
Nishimura A, Akahoshi T, Takahashi M, et al. Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. J Leukoc Biol 1997; 62(4): 444-9.
[] [PMID: 9335313]
Klimatcheva E, Pandina T, Reilly C, et al. CXCL13 antibody for the treatment of autoimmune disorders. BMC Immunol 2015; 16: 6.
[] [PMID: 25879435]
Zimmerman DH, Taylor P, Bendele A, et al. CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model. Int Immunopharmacol 2010; 10(4): 412-21.
[] [PMID: 20074669]
Zhong C, Wang J, Li B, et al. Development and preclinical characterization of a humanized antibody targeting CXCL12. Clin Cancer Res 2013; 19(16): 4433-45.
[] [PMID: 23812669]
Revesz L, Bollbuck B, Buhl T, et al. Novel CCR1 antagonists with oral activity in the mouse collagen induced arthritis. Bioorg Med Chem Lett 2005; 15(23): 5160-4.
[] [PMID: 16198561]
Brühl H, Cihak J, Plachý J, et al. Targeting of Gr-1+,CCR2+ monocytes in collagen-induced arthritis. Arthritis Rheum 2007; 56(9): 2975-85.
[] [PMID: 17763443]
Min SH, Wang Y, Gonsiorek W, et al. Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model of arthritis. Biochem Biophys Res Commun 2010; 391(1): 1080-6.
[] [PMID: 20004647]
Moschovakis GL, Bubke A, Friedrichsen M, et al. The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy. Cell Mol Immunol 2018.
[] [PMID: 29973648]
Gong JH, Yan R, Waterfield JD, Clark-Lewis I. Post-onset inhibition of murine arthritis using combined chemokine antagonist therapy. Rheumatology (Oxford) 2004; 43(1): 39-42.
[] [PMID: 14566030]
Duan H, Yang P, Fang F, Ding S, Xiao W. CCR5 small interfering RNA ameliorated joint inflammation in rats with adjuvant-induced arthritis. Immunol Lett 2014; 162(2 Pt B): 258-63.
[] [PMID: 25300256]
Lan YY, Wang YQ, Liu Y. CCR5 silencing reduces inflammatory response, inhibits viability, and promotes apoptosis of synovial cells in rat models of rheumatoid arthritis through the MAPK signaling pathway. J Cell Physiol 2019.
[] [PMID: 31066041]
Podolin PL, Bolognese BJ, Foley JJ, et al. A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol 2002; 169(11): 6435-44.
[] [PMID: 12444152]
Mohan K, Issekutz TB. Blockade of chemokine receptor CXCR3 inhibits T cell recruitment to inflamed joints and decreases the severity of adjuvant arthritis. J Immunol 2007; 179(12): 8463-9.
[] [PMID: 18056393]
Manjavachi MN, Quintão NL, Campos MM, et al. The effects of the selective and non-peptide CXCR2 receptor antagonist SB225002 on acute and long-lasting models of nociception in mice. Eur J Pain 2010; 14(1): 23-31.
[] [PMID: 19264522]
Amat M, Benjamim CF, Williams LM, et al. Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo. Br J Pharmacol 2006; 149(6): 666-75.
[] [PMID: 17016504]
Matsukawa A, Yoshimura T, Fujiwara K, Maeda T, Ohkawara S, Yoshinaga M. Involvement of growth-related protein in lipopolysaccharide-induced rabbit arthritis: Cooperation between growth-related protein and IL-8, and interrelated regulation among TNFalpha, IL-1, IL-1 receptor antagonist, IL-8, and growth-related protein. Lab Invest 1999; 79(5): 591-600.
[PMID: 10334570]
Youssef S, Maor G, Wildbaum G, Grabie N, Gour-Lavie A, Karin N. C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis. J Clin Invest 2000; 106(3): 361-71.
[] [PMID: 10930439]
Clanchy FIL, Williams RO. Ibudilast inhibits chemokine expression in rheumatoid arthritis synovial fibroblasts and exhibits immunomodulatory activity in experimental arthritis. Arthritis Rheumatol 2019; 71(5): 703-11.
[] [PMID: 30474934]
Gao P, Zhou XY, Yashiro-Ohtani Y, et al. The unique target specificity of a nonpeptide chemokine receptor antagonist: Selective blockade of two Th1 chemokine receptors CCR5 and CXCR3. J Leukoc Biol 2003; 73(2): 273-80.
[] [PMID: 12554804]
Cunha TM, Barsante MM, Guerrero AT, et al. Treatment with DF 2162, a non-competitive allosteric inhibitor of CXCR1/2, diminishes neutrophil influx and inflammatory hypernociception in mice. Br J Pharmacol 2008; 154(2): 460-70.
[] [PMID: 18362895]
Han Y, Li X, Zhou Q, et al. FTY720 Abrogates collagen-induced arthritis by hindering dendritic cell migration to local lymph nodes. J Immunol 2015; 195(9): 4126-35.
[] [PMID: 26416269]
Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis 2016; 75(4): 730-8.
[] [PMID: 26613766]
Krishnamurthy A, Joshua V, Haj Hensvold A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis 2016; 75(4): 721-9.
[] [PMID: 26612338]
Zapico I, Coto E, Rodríguez A, Alvarez C, Torre JC, Alvarez V. CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis. Genes Immun 2000; 1(4): 288-9.
[] [PMID: 11196706]
Yellin M, Paliienko I, Balanescu A, et al. A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2012; 64(6): 1730-9.
[] [PMID: 22147649]
Kennedy WP, Simon JA, Offutt C, et al. Efficacy and safety of pateclizumab (anti-lymphotoxin-α) compared to adalimumab in rheumatoid arthritis: A head-to-head phase 2 randomized controlled study (The ALTARA Study). Arthritis Res Ther 2014; 16(5): 467.
[] [PMID: 25359150]
Emu B, Luca D, Offutt C, et al. Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α: Results of a phase I randomized, placebo-controlled trial. Arthritis Res Ther 2012; 14(1): R6.
[] [PMID: 22225620]
Bao J, Liu W, Bao YX. Recombinant human interleukin receptor antagonist influences serum chemokines in patients with rheumatoid arthritis. Cent Eur J Immunol 2014; 39(2): 170-3.
[] [PMID: 26155119]
Boyle DL, Soma K, Hodge J, et al. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis 2015; 74(6): 1311-6.
[] [PMID: 25398374]
Lebre MC, Vergunst CE, Choi IY, et al. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis. PLoS One 2011; 6(7)e21772
[] [PMID: 21747955]
Gladue RP, Brown MF, Zwillich SH. CCR1 antagonists: What have we learned from clinical trials. Curr Top Med Chem 2010; 10(13): 1268-77.
[] [PMID: 20536425]
Vergunst CE, Gerlag DM, von Moltke L, et al. MLN3897 plus methotrexate in patients with rheumatoid arthritis: Safety, efficacy, pharmacokinetics, and pharmacodynamics of an oral CCR1 antagonist in a phase IIa, double-blind, placebo-controlled, randomized, proof-of-concept study. Arthritis Rheum 2009; 60(12): 3572-81.
[] [PMID: 19950299]
Strunz AK, Zweemer AJ, Weiss C, et al. Synthesis and biological evaluation of spirocyclic antagonists of CCR2 (chemokine CC receptor subtype 2). Bioorg Med Chem 2015; 23(14): 4034-49.
[] [PMID: 25766632]
Gerlag DM, Hollis S, Layton M, et al. Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate. Arthritis Rheum 2010; 62(11): 3154-60.
[] [PMID: 20662070]
De Klerck B, Geboes L, Hatse S, et al. Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther 2005; 7(6): R1208-20.
[] [PMID: 16277673]
Tamamura H, Tsutsumi H, Masuno H, Fujii N. Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra- and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis. Curr Med Chem 2007; 14(1): 93-102.
[] [PMID: 17266570]
Balasubramanian PK, Balupuri A, Kothandan G, Cho SJ. In silico study of 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl) ethanones derivatives as CCR1 antagonist: homology modeling, docking and 3D-QSAR approach. Bioorg Med Chem Lett 2014; 24(3): 928-33.
[] [PMID: 24424131]
Wang Y, Wei D, Lai Z, Le Y. Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis. Int Immunopharmacol 2006; 6(12): 1825-32.
[] [PMID: 17052673]
Marotte H, Ruth JH, Campbell PL, Koch AE, Ahmed S. Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis. Rheumatology (Oxford) 2010; 49(3): 467-79.
[] [PMID: 20032224]
Garcia Ede F, de Oliveira MA, Candido LC, et al. Effect of the hydroethanolic extract from Echinodorus grandiflorus leaves and a fraction enriched in flavone-C-glycosides on antigen-induced arthritis in mice. Planta Med 2016; 82(5): 407-13.
[] [PMID: 26824620]
Ahmad SF, Attia SM, Zoheir KM, Ashour AE, Bakheet SA. Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide treatment. Int Immunopharmacol 2014; 19(1): 52-9.
[] [PMID: 24444779]
Odai T, Matsunawa M, Takahashi R, et al. Correlation of CX3CL1 and CX3CR1 levels with response to infliximab therapy in patients with rheumatoid arthritis. J Rheumatol 2009; 36(6): 1158-65.
[] [PMID: 19369458]
Kawashiri SY, Kawakami A, Iwamoto N, et al. Proinflammatory cytokines synergistically enhance the production of chemokine ligand 20 (CCL20) from rheumatoid fibroblast-like synovial cells in vitro and serum CCL20 is reduced in vivo by biologic disease-modifying antirheumatic drugs. J Rheumatol 2009; 36(11): 2397-402.
[] [PMID: 19797510]
Rosengren S, Wei N, Kalunian KC, Kavanaugh A, Boyle DL. CXCL13: A novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis. Rheumatology (Oxford) 2011; 50(3): 603-10.
[] [PMID: 21098574]
Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J. Serum chemokines in patients with rheumatoid arthritis treated with etanercept. Rheumatol Int 2011; 31(4): 457-61.
[] [PMID: 20024555]
Lin YC, Lin YC, Huang MY, et al. Tumor necrosis factor-alpha inhibitors suppress CCL2 chemokine in monocytes via epigenetic modification. Mol Immunol 2017; 83: 82-91.
[] [PMID: 28113136]
Umemura M, Isozaki T, Ishii S, et al. Reduction of serum ADAM17 level accompanied with decreased cytokines after abatacept therapy in patients with rheumatoid arthritis. Int J Biomed Sci 2014; 10(4): 229-35.
[PMID: 25598752]
Aeberli D, Kamgang R, Balani D, Hofstetter W, Villiger PM, Seitz M. Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis. RMD Open 2016; 2(1)e000079
[] [PMID: 26819749]
Aerts NE, De Knop KJ, Leysen J, et al. Increased IL-17 production by peripheral T helper cells after tumour necrosis factor blockade in rheumatoid arthritis is accompanied by inhibition of migration-associated chemokine receptor expression. Rheumatology (Oxford) 2010; 49(12): 2264-72.
[] [PMID: 20724433]
Han BK, Kuzin I, Gaughan JP, Olsen NJ, Bottaro A. Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhibitor therapy in patients with moderate to severe rheumatoid arthritis: A pilot, prospective study. Arthritis Res Ther 2016; 18: 93.
[] [PMID: 27102921]
Ospelt C, Kurowska-Stolarska M, Neidhart M, et al. The dual inhibitor of lipoxygenase and cyclooxygenase ML3000 decreases the expression of CXCR3 ligands. Ann Rheum Dis 2008; 67(4): 524-9.
[] [PMID: 17666446]
Cesaro A, Anceriz N, Plante A, Pagé N, Tardif MR, Tessier PA. An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. PLoS One 2012; 7(9)e45478
[] [PMID: 23029038]
Marino F, Maresca AM, Castiglioni L, et al. Simvastatin down-regulates the production of interleukin-8 by neutrophil leukocytes from dyslipidemic patients. BMC Cardiovasc Disord 2014; 14: 37.
[] [PMID: 24629144]
Pereira MM, Santos TP, Aras R, Couto RD, Atta ML, Atta AM. Serum levels of cytokines and chemokines associated with cardiovascular disease in Brazilian patients treated with statins for dyslipidemia. Int Immunopharmacol 2014; 18(1): 66-70.
[] [PMID: 24252254]
Impellizzeri D, Di Paola R, Cordaro M, et al. Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation. Biochem Pharmacol 2016; 119: 27-41.
[] [PMID: 27599446]
Di Paola R, Fusco R, Impellizzeri D, et al. Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats. Arthritis Res Ther 2016; 18(1): 291.
[] [PMID: 27955699]
Hounoki H, Sugiyama E, Mohamed SG, et al. Activation of peroxisome proliferator-activated receptor gamma inhibits TNF-alpha-mediated osteoclast differentiation in human peripheral monocytes in part via suppression of monocyte chemoattractant protein-1 expression. Bone 2008; 42(4): 765-74.
[] [PMID: 18242157]
Choi J, Kim SH, Kim S. Suppressive effects of PG201, an antiarthritic botanical formulation, on lipopolysaccharide-induced inflammatory mediators in Raw264.7 cells. Exp Biol Med (Maywood) 2012; 237(5): 499-508.
[] [PMID: 22442340]
Yang RC, Chang CC, Sheen JM, Wu HT, Pang JH, Huang ST. Davallia bilabiata inhibits TNF-α-induced adhesion molecules and chemokines by suppressing IKK/NF-kappa B pathway in vascular endothelial cells. Am J Chin Med 2014; 42(6): 1411-29.
[] [PMID: 25482674]
Rosengren S, Corr M, Firestein GS, Boyle DL. 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 2012; 71(3): 440-7.
[] [PMID: 22121136]
Yoon CH, Chung SJ, Lee SW, Park YB, Lee SK, Park MC. Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proinflammatory gene expressions in rheumatoid arthritis fibroblast-like synoviocytes. Joint Bone Spine 2013; 80(3): 274-9.
[] [PMID: 23058179]
Rosas EC, Correa LB, Pádua Tde A, et al. Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis. J Ethnopharmacol 2015; 175: 490-8.
[] [PMID: 26453933]
Schmidt N, Art J, Forsch I, et al. The anti-inflammatory fungal compound (S)-curvularin reduces proinflammatory gene expression in an in vivo model of rheumatoid arthritis. J Pharmacol Exp Ther 2012; 343(1): 106-14.
[] [PMID: 22767531]
Turner-Brannen E, Choi KY, Lippert DN, et al. Modulation of interleukin-1β-induced inflammatory responses by a synthetic cationic innate defence regulator peptide, IDR-1002, in synovial fibroblasts. Arthritis Res Ther 2011; 13(4): R129.
[] [PMID: 21835002]
Yoshimura S, Asano K, Nakane A. Attenuation of collagen-induced arthritis in mice by salmon proteoglycan. BioMed Res Int 2014; 2014406453
[] [PMID: 25032213]
Li G, Cunin P, Wu D, et al. The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1. PLoS Genet 2016; 12(9)e1006292
[] [PMID: 27626929]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy