Top

BioDrugs

Published in:

01-05-2004 | Novel Therapeutic Strategies

New Drug Targets in Rheumatoid Arthritis

Focus on Chemokines

Author: Dr Katrine R. Shadidi

Published in: BioDrugs | Issue 3/2004

Abstract

Rheumatoid arthritis is a chronic inflammatory disease where the synovial tissue is characterized by heavy infiltration of leukocytes. Chemokines and chemokine receptors play an important role in cell migration and positioning of leukocytes within the inflamed rheumatoid synovium. There is now much focus on the specific contribution and role of each chemokine and chemokine receptor in the chronic inflammatory process in the synovial tissue. Recent evidence indicates that interference with the chemokines released from the inflamed synovial cells or the chemokine receptors expressed on the cells infiltrating the synovial tissue may lead to discovery of new therapeutics for this disease.

Panayi GS, Corrigall VM, Pitzalis C. Pathogenesis of rheumatoid arthritis: the role of T cells and other beasts. Rheum Dis Clin North Am 2001 May; 27(2): 317–34PubMedCrossRef

McInnes IB, Leung BP, Liew FY. Cell-cell interactions in synovitis: interactions between T lymphocytes and synovial cells. Arthritis Res 2000 Jul; 2(5): 374–8PubMedCrossRef

Bodolay E, Koch AE, Kim J, et al. Angiogenesis and chemokines in rheumatoid arthritis and other systemic inflammatory rheumatic diseases. J Cell Mol Med 2002 Jul–Sep; 6(3): 357–76PubMedCrossRef

Koch AE. Review: angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum 1998 Jun; 41(6): 951–62PubMedCrossRef

Kurosaka M, Ziff M. Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium. J Exp Med 1983 Oct; 158(4): 1191–210PubMedCrossRef

Randen I, Mellbye OJ, Forre O, et al. The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue. Scand J Immunol 1995 May; 41(5): 481–6PubMedCrossRef

Harris ED. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med 1990 May; 322(18): 1277–89PubMedCrossRef

Szekanecz Z, Kim J, Koch AE. Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol 2003 Feb; 15(1): 15–21PubMedCrossRef

Szekanecz Z, Koch AE. Chemokines and angiogenesis. Curr Opin Rheumatol 2001 May; 13(3): 202–8PubMedCrossRef

10.

Buckley CD. Why does chronic inflammatory joint disease persist? Clin Med 2003 Jul–Aug; 3(4): 361–6PubMed

11.

Loetscher P, Moser B. Homing chemokines in rheumatoid arthritis. Arthritis Res 2002; 4(4): 233–6PubMedCrossRef

12.

Tanaka Y. Integrin activation by chemokines: relevance to inflammatory adhesion cascade during T cell migration. Histol Histopathol 2000 Oct; 15(4): 1169–76PubMed

13.

Butcher EC, Williams M, Youngman K, et al. Lymphocyte trafficking and regional immunity. Adv Immunol 1999; 72: 209–53PubMedCrossRef

14.

D’Ambrosio D, Albanesi C, Lang R, et al. Quantitative differences in chemokine receptor engagement generate diversity in integrin-dependent lymphocyte adhesion. J Immunol 2002 Sep; 169(5): 2303–12PubMed

15.

Savill J, Fadok V. Corpse clearance defines the meaning of cell death. Nature 2000 Oct 12; 407(6805): 784–8PubMedCrossRef

16.

Akbar AN, Salmon M. Cellular environments and apoptosis: tissue microenvironments control activated T-cell death. Immunol Today 1997 Feb; 18(2): 72–6PubMedCrossRef

17.

Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity 2000 Feb; 12(2): 121–7PubMedCrossRef

18.

Shadidi KR, Aarvak T, Henriksen JE, et al. The chemokines CCL5, CCL2 and CXCL12 play significant roles in the migration of Th1 cells into rheumatoid synovial tissue. Scand J Immunol 2003 Feb; 57(2): 192–8PubMedCrossRef

19.

Ruth JH, Rottman JB, Katschke KJ, et al. Selective lymphocyte chemokine receptor expression in the rheumatoid joint. Arthritis Rheum 2001 Dec; 44(12): 2750–60PubMedCrossRef

20.

Takemura S, Braun A, Crowson C, et al. Lymphoid neogenesis in rheumatoid synovitis. J Immunol 2001 Jul 15; 167(2): 1072–80PubMed

21.

Pablos JL, Santiago B, Galindo M, et al. Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol 2003 Feb; 170(4): 2147–52PubMed

22.

Katschke KJ, Rottman JB, Ruth JH, et al. Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis. Arthritis Rheum 2001 May; 44(5): 1022–32PubMedCrossRef

23.

Haringman JJ, Kraan MC, Smeets TJ, et al. Chemokine blockade and chronic inflammatory disease: proof of concept in patients with rheumatoid arthritis. Ann Rheum Dis 2003 Aug; 62(8): 715–21PubMedCrossRef

24.

Bruhl H, Wagner K, Kellner H, et al. Surface expression of CC- and CXC-chemokine receptors on leucocyte subsets in inflammatory joint diseases. Clin Exp Immunol 2001 Dec; 126(3): 551–9PubMedCrossRef

25.

Hayashida K, Nanki T, Girschick H, et al. Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8. Arthritis Res 2001; 3(2): 118–26PubMedCrossRef

26.

Yoneyama H, Harada A, Imai T, et al. Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice. J Clin Invest 1998 Dec; 102(11): 1933–41PubMedCrossRef

27.

Wedderburn LR, Robinson N, Patel A, et al. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum 2000 Apr; 43(4): 765–74PubMedCrossRef

28.

Cravens PD, Lipsky PE. Dendritic cells, chemokine receptors and autoimmune inflammatory diseases. Immunol Cell Biol 2002 Oct; 80(5): 497–505PubMedCrossRef

29.

Matsui T, Akahoshi T, Namai R, et al. Selective recruitment of CCR6-expressing cells by increased production of MIP-3alpha in rheumatoid arthritis. Clin Exp Immunol 2001 Jul; 125(1): 155–61PubMedCrossRef

30.

Hjelmstrom P. Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines. J Leukoc Biol 2001 Mar; 69(3): 331–9PubMed

31.

Weyand CM, Goronzy JJ. Ectopic germinal center formation in rheumatoid synovitis. Ann N Y Acad Sci 2003 Apr; 987: 140–9PubMedCrossRef

32.

Walz A, Kunkel SL, Streier RM. CXC chemokines: an overview. In: Koch AE, Streier RM, editors. Chemokines in disease. Austin (TX): RG Landers Company, 1996: 1–25

33.

Falcone M, Sarvetnick N. Cytokines that regulate autoimmune responses. Curr Opin Immunol 1999 Dec; 11(6): 670–6PubMedCrossRef

34.

Sallusto F, Kremmer E, Palermo B, et al. Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells. Eur J Immunol 1999 Jun; 29(6): 2037–45PubMedCrossRef

35.

Keane MP, Strieter RM. The role of CXC chemokines in the regulation of angiogenesis. Chem Immunol 1999; 72: 86–101PubMedCrossRef

36.

Kasama T, Strieter RM, Lukacs NW, et al. Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J Clin Invest 1995 Jun; 95(6): 2868–76PubMedCrossRef

37.

Nanki T, Hayashida K, El-Gabalawy HS, et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium. J Immunol 2000 Dec; 165(11): 6590–8PubMed

38.

Bradfield PF, Amft N, Vernon-Wilson E, et al. Rheumatoid fibroblast-like synoviocytes overexpress the chemokine stromal cell-derived factor 1 (CXCL12), which supports distinct patterns and rates of CD4+ and CD8+ T cell migration within synovial tissue. Arthritis Rheum 2003 Sep; 48(9): 2472–82PubMedCrossRef

39.

Burger JA, Zvaifler NJ, Tsukada N, et al. Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism. J Clin Invest 2001 Feb; 107(3): 305–15PubMedCrossRef

40.

Ogata H, Takeya M, Yoshimura T, et al. The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats. J Pathol 1997 May; 182(1): 106–14PubMedCrossRef

41.

Kim CH, Kunkel EJ, Boisvert J, et al. Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest 2001 Mar; 107(5): 595–601PubMedCrossRef

42.

Nanki T, Imai T, Nagasaka K, et al. Migration of CX3CRl-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis. Arthritis Rheum 2002 Nov; 46(11): 2878–83PubMedCrossRef

43.

Ruth JH, Volin MV, Haines GK, et al. Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 2001 Jul; 44(7): 1568–81PubMedCrossRef

44.

Campbell JJ, Butcher EC. Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. Curr Opin Immunol 2000 Jun; 12(3): 336–41PubMedCrossRef

45.

Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 2000; 18: 593–620PubMedCrossRef

46.

Thelen M. Dancing to the tune of chemokines. Nat Immunol 2001 Feb; 2(2): 129–34PubMedCrossRef

47.

Mantovani A. The chemokine system: redundancy for robust outputs. Immunol Today 1999 Jun; 20(6): 254–7PubMedCrossRef

48.

Dolhain RJ, van der Heiden AN, ter Haar NT, et al. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum 1996 Dec; 39(12): 1961–9PubMedCrossRef

49.

Bonecchi R, Bianchi G, Bordignon PP, et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998 Jan; 187(1): 129–34PubMedCrossRef

50.

Annunziato F, Galli G, Cosmi L, et al. Molecules associated with human Thl or Th2 cells. Eur Cytokine Netw 1998; 9Suppl. 5: 12–6PubMed

51.

Orteu CH, Poulter LW, Rustin MH, et al. The role of apoptosis in the resolution of T cell-mediated cutaneous inflammation. J Immunol 1998 Aug; 161(4): 1619–29PubMed

52.

Patel DD, Zachariah JP, Whichard LP. CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol 2001 Jan; 98(1): 39–45PubMedCrossRef

53.

Volin MV, Shah MR, Tokuhira M, et al. RANTES expression and contribution to monocyte chemotaxis in arthritis. Clin Immunol Immunopathol 1998 Oct; 89(1): 44–53PubMedCrossRef

54.

Suzuki N, Nakajima A, Yoshino S, et al. Selective accumulation of CCR5+ T lymphocytes into inflamed joints of rheumatoid arthritis. Int Immunol 1999 Apr; 11(4): 553–9PubMedCrossRef

55.

Barnes DA, Tse J, Kaufhold M, et al. Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J Clin Invest 1998 Jun; 101(12): 2910–9PubMedCrossRef

56.

Robinson E, Keystone EC, Schall TJ, et al. Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells. Clin Exp Immunol 1995 Sep; 101(3): 398–407PubMedCrossRef

57.

al-Mughales J, Blyth TH, Hunter JA, et al. The chemoattractant activity of rheumatoid synovial fluid for human lymphocytes is due to multiple cytokines. Clin Exp Immunol 1996 Nov; 106(2): 230–6PubMedCrossRef

58.

Thornton S, Duwel LE, Boivin GP, et al. Association of the course of collagen-induced arthritis with distinct patterns of cytokine and chemokine messenger RNA expression. Arthritis Rheum 1999 Jun; 42(6): 1109–18PubMedCrossRef

59.

Strieter RM, Polverini PJ, Kunkel SL, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 1995 Nov; 270(45): 27348–57PubMedCrossRef

60.

Addison CL, Daniel TO, Burdick MD, et al. The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity. J Immunol 2000 Nov; 165(9): 5269–77PubMed

61.

Volin MV, Woods JM, Amin MA, et al. Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis. Am J Pathol 2001 Oct; 159(4): 1521–30PubMedCrossRef

62.

Salcedo R, Ponce ML, Young HA, et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 2000 Jul; 96(1): 34–40PubMed

63.

Nanki T, Nagasaka K, Hayashida K, et al. Chemokines regulate IL-6 and IL-8 production by fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Immunol 2001 Nov; 167(9): 5381–5PubMed

64.

Pilling D, Akbar AN, Girdlestone J, et al. Interferon-beta mediates stromal cell rescue of T cells from apoptosis. Eur J Immunol 1999 Mar; 29(3): 1041–50PubMedCrossRef

65.

Qin S, Rottman JB, Myers P, et al. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 1998 Feb; 101(4): 746–54PubMedCrossRef

66.

Finkelman FD, Urban JFJ. The other side of the coin: the protective role of the TH2 cytokines. J Allergy Clin Immunol 2001 May; 107(5): 772–80PubMedCrossRef

67.

Koch AE, Kunkel SL, Shah MR, et al. Growth-related gene product alpha: a chemotactic cytokine for neutrophils in rheumatoid arthritis. J Immunol 1995 Oct; 155(7): 3660–6PubMed

68.

Matsukawa A, Yoshimura T, Miyamoto K, et al. Analysis of the inflammatory cytokine network among TNF alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis. Lab Invest 1997 May; 76(5): 629–38PubMed

69.

Salomon I, Netzer N, Wildbaum G, et al. Targeting the function of IFN-gamma-inducible protein 10 suppresses ongoing adjuvant arthritis. J Immunol 2002 Sep; 169(5): 2685–93PubMed

70.

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 Jun; 162(12): 7492–500PubMed

71.

Xie JH, Nomura N, Lu M, et al. Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation. J Leukoc Biol 2003 Jun; 73(6): 771–80PubMedCrossRef

72.

Rodriguez-Wilhelmi P, Montes R, Matsukawa A, et al. Tumor necrosis factor-alpha inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock. J Lab Clin Med 2003 Apr; 141(4): 257–64PubMedCrossRef

73.

Youssef S, Maor G, Wildbaum G, et al. C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis. Clin Invest 2000 Aug; 106(3): 361–71CrossRef

74.

Gong JH, Ratkay LG, Waterfield JD, et al. Monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model. J Exp Med 1997 Jul; 186(1): 131–7PubMedCrossRef

75.

Wooley PH, Schaefer C, Whalen JD, et al. A peptide sequence from platelet factor 4 (CT-112) is effective in the treatment of type II collagen induced arthritis in mice. J Rheumatol 1997 May; 24(5): 890–8PubMed

76.

Matthys P, Hatse S, Vermeire K, et al. AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice. J Immunol 2001 Oct 15; 167(8): 4686–92PubMed

77.

Yang YF, Mukai T, Gao P, et al. A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses. Eur J Immunol 2002 Aug; 32(8): 2124–32PubMedCrossRef

78.

Taylor PC, Peters AM, Paleolog E, et al. Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. Arthritis Rheum 2000 Jan; 43(1): 38–47PubMedCrossRef

Title: New Drug Targets in Rheumatoid Arthritis
Focus on Chemokines
Author: Dr Katrine R. Shadidi
Publication date: 01-05-2004
Publisher: Springer International Publishing
Published in: BioDrugs / Issue 3/2004
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI: https://doi.org/10.2165/00063030-200418030-00004

Keynote webinar | Spotlight on medication adherence

Springer Medicine

New Drug Targets in Rheumatoid Arthritis

Focus on Chemokines

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2004

Spotlight on Imatinib Mesylate in Chronic Myeloid Leukemia

Electroporation for Gene Transfer to Skeletal Muscles

Etanercept

Is There a Future for Neural Transplantation?

Kinase Targets and Inhibitors for the Treatment of Airway Inflammatory Diseases

Etanercept