Abstract
Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA), whereas the mechanisms for constitutive production of inflammatory cytokines in affected joints are largely unknown. Recently, integrin-mediated interaction with extracellular matrix (ECM) proteins has been demonstrated to play a role in regulating cytokine production in T cells and monocytes. In this study, we investigated the contribution of the beta 1 integrin-mediated interaction with ECM proteins to the persistent cytokine gene expression in RA synovial fluid mononuclear cells (SFMNC). We examined mRNA expression of 14 cytokines in the SFMNC of three RA patients, which were either fresh or cultured overnight in serum-free medium on ECM-coated plates, by polymerase chain reaction with a panel of oligonucleotide primers specific for each cytokine. The persistent expression of various cytokine mRNA found in fresh SFMNC was maintained after overnight culture in serum-free medium on ECM proteins, especially on laminin (LM), but not on serum albumin. This effect of LM was inhibited by an anti-integrin beta 1 chain (CD29) mAb, as well as by an anti-CD3 mAb, indicating an important role of the beta 1 integrin- mediated interaction with ECM proteins in regulating persistent cytokine gene expression in RA SFMNC, and a key role of T cells in regulating inflammatory monokine production.
Full Text
The Full Text of this article is available as a PDF (925.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akira S., Hirano T., Taga T., Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990 Aug;4(11):2860–2867. [PubMed] [Google Scholar]
- Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
- Brennan F. M., Chantry D., Jackson A., Maini R., Feldmann M. Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet. 1989 Jul 29;2(8657):244–247. doi: 10.1016/s0140-6736(89)90430-3. [DOI] [PubMed] [Google Scholar]
- Brennan F. M., Zachariae C. O., Chantry D., Larsen C. G., Turner M., Maini R. N., Matsushima K., Feldmann M. Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. Eur J Immunol. 1990 Sep;20(9):2141–2144. doi: 10.1002/eji.1830200938. [DOI] [PubMed] [Google Scholar]
- Buchan G., Barrett K., Turner M., Chantry D., Maini R. N., Feldmann M. Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha. Clin Exp Immunol. 1988 Sep;73(3):449–455. [PMC free article] [PubMed] [Google Scholar]
- Dubravec D. B., Spriggs D. R., Mannick J. A., Rodrick M. L. Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6758–6761. doi: 10.1073/pnas.87.17.6758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feldmann M., Brennan F. M., Chantry D., Haworth C., Turner M., Katsikis P., Londei M., Abney E., Buchan G., Barrett K. Cytokine assays: role in evaluation of the pathogenesis of autoimmunity. Immunol Rev. 1991 Feb;119:105–123. doi: 10.1111/j.1600-065x.1991.tb00580.x. [DOI] [PubMed] [Google Scholar]
- Ferm M. T., Söderström K., Jindal S., Grönberg A., Ivanyi J., Young R., Kiessling R. Induction of human hsp60 expression in monocytic cell lines. Int Immunol. 1992 Mar;4(3):305–311. doi: 10.1093/intimm/4.3.305. [DOI] [PubMed] [Google Scholar]
- Firestein G. S., Alvaro-Gracia J. M., Maki R., Alvaro-Garcia J. M. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 1990 May 1;144(9):3347–3353. [PubMed] [Google Scholar]
- Geppert T. D., Davis L. S., Gur H., Wacholtz M. C., Lipsky P. E. Accessory cell signals involved in T-cell activation. Immunol Rev. 1990 Oct;117:5–66. doi: 10.1111/j.1600-065x.1990.tb00566.x. [DOI] [PubMed] [Google Scholar]
- Harris E. D., Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277–1289. doi: 10.1056/NEJM199005033221805. [DOI] [PubMed] [Google Scholar]
- Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
- Haworth C., Brennan F. M., Chantry D., Turner M., Maini R. N., Feldmann M. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur J Immunol. 1991 Oct;21(10):2575–2579. doi: 10.1002/eji.1830211039. [DOI] [PubMed] [Google Scholar]
- Hemler M. E., Glass D., Coblyn J. S., Jacobson J. G. Very late activation antigens on rheumatoid synovial fluid T lymphocytes. Association with stages of T cell activation. J Clin Invest. 1986 Sep;78(3):696–702. doi: 10.1172/JCI112629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
- Hermann E., Lohse A. W., Van der Zee R., Van Eden W., Mayet W. J., Probst P., Poralla T., Meyer zum Büschenfelde K. H., Fleischer B. Synovial fluid-derived Yersinia-reactive T cells responding to human 65-kDa heat-shock protein and heat-stressed antigen-presenting cells. Eur J Immunol. 1991 Sep;21(9):2139–2143. doi: 10.1002/eji.1830210923. [DOI] [PubMed] [Google Scholar]
- Koga T., Wand-Württenberger A., DeBruyn J., Munk M. E., Schoel B., Kaufmann S. H. T cells against a bacterial heat shock protein recognize stressed macrophages. Science. 1989 Sep 8;245(4922):1112–1115. doi: 10.1126/science.2788923. [DOI] [PubMed] [Google Scholar]
- Landis R. C., Friedman M. L., Fisher R. I., Ellis T. M. Induction of human monocyte IL-1 mRNA and secretion during anti-CD3 mitogenesis requires two distinct T cell-derived signals. J Immunol. 1991 Jan 1;146(1):128–135. [PubMed] [Google Scholar]
- Marucha P. T., Zeff R. A., Kreutzer D. L. Cytokine regulation of IL-1 beta gene expression in the human polymorphonuclear leukocyte. J Immunol. 1990 Nov 1;145(9):2932–2937. [PubMed] [Google Scholar]
- Mueller D. L., Jenkins M. K., Schwartz R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. doi: 10.1146/annurev.iy.07.040189.002305. [DOI] [PubMed] [Google Scholar]
- Nojima Y., Rothstein D. M., Sugita K., Schlossman S. F., Morimoto C. Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein. J Exp Med. 1992 Apr 1;175(4):1045–1053. doi: 10.1084/jem.175.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ofosu-Appiah W. A., Warrington R. J., Wilkins J. A. Interleukin 2 responsive T cell clones from rheumatoid and normal subjects: proliferative responses to connective tissue elements. Clin Immunol Immunopathol. 1989 Feb;50(2):264–271. doi: 10.1016/0090-1229(89)90134-7. [DOI] [PubMed] [Google Scholar]
- Ofosu-Appiah W., Warrington R. J., Morgan K., Wilkins J. A. Lymphocyte extracellular matrix interactions. Induction of interferon by connective tissue components. Scand J Immunol. 1989 May;29(5):517–525. doi: 10.1111/j.1365-3083.1989.tb01154.x. [DOI] [PubMed] [Google Scholar]
- Pitzalis C., Kingsley G., Haskard D., Panayi G. The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion. Eur J Immunol. 1988 Sep;18(9):1397–1404. doi: 10.1002/eji.1830180915. [DOI] [PubMed] [Google Scholar]
- Pitzalis C., Kingsley G., Lanchbury J. S., Murphy J., Panayi G. S. Expression of HLA-DR, DQ and DP antigens and interleukin-2 receptor on synovial fluid T lymphocyte subsets in rheumatoid arthritis: evidence for "frustrated" activation. J Rheumatol. 1987 Aug;14(4):662–666. [PubMed] [Google Scholar]
- Roberts K., Yokoyama W. M., Kehn P. J., Shevach E. M. The vitronectin receptor serves as an accessory molecule for the activation of a subset of gamma/delta T cells. J Exp Med. 1991 Jan 1;173(1):231–240. doi: 10.1084/jem.173.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimizu Y., van Seventer G. A., Horgan K. J., Shaw S. Roles of adhesion molecules in T-cell recognition: fundamental similarities between four integrins on resting human T cells (LFA-1, VLA-4, VLA-5, VLA-6) in expression, binding, and costimulation. Immunol Rev. 1990 Apr;114:109–143. doi: 10.1111/j.1600-065x.1990.tb00563.x. [DOI] [PubMed] [Google Scholar]
- Strober S., Holoshitz J. Mechanisms of immune injury in rheumatoid arthritis: evidence for the involvement of T cells and heat-shock protein. Immunol Rev. 1990 Dec;118:233–255. doi: 10.1111/j.1600-065x.1990.tb00818.x. [DOI] [PubMed] [Google Scholar]
- Takahashi K., Nakamura T., Adachi H., Yagita H., Okumura K. Antigen-independent T cell activation mediated by a very late activation antigen-like extracellular matrix receptor. Eur J Immunol. 1991 Jun;21(6):1559–1562. doi: 10.1002/eji.1830210634. [DOI] [PubMed] [Google Scholar]
- Wasik M. A., Donnelly R. P., Beller D. I. Lymphokine-independent induction of macrophage membrane IL-1 by autoreactive T cells recognizing either class I or class II MHC determinants. J Immunol. 1988 Nov 15;141(10):3456–3462. [PubMed] [Google Scholar]
- Yamada A., Nikaido T., Nojima Y., Schlossman S. F., Morimoto C. Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor. J Immunol. 1991 Jan 1;146(1):53–56. [PubMed] [Google Scholar]
- Yurochko A. D., Liu D. Y., Eierman D., Haskill S. Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9034–9038. doi: 10.1073/pnas.89.19.9034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Eden W. Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis. Immunol Rev. 1991 Jun;121:5–28. doi: 10.1111/j.1600-065x.1991.tb00821.x. [DOI] [PubMed] [Google Scholar]