Multifaceted role of TNF-α during the pathogenesis of rheumatoid arthritis

Ramanjaneya V. R. Mula, Rangaiah Shashidharamurthy

Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine, School of Pharmacy, Suwanee, USA.

DOI: 10.4236/abb.2013.410123                

Abstract

Tumor necrosis factor alpha (TNF-α) a cytokine has been shown to be the key player during the pathogenesis of several autoimmune inflammatory disorders (presumably sterile inflammation) including rheumatoid arthritis (RA). Several studies have shown that TNF-α is mainly involved in the proinflammatory responses. However recent studies have reported multifunctional role of TNF-α during the development of RA. Therefore, in this article we have highlighted the distinct functions of TNF-α during pathogenesis of RA.  

Keywords

Cytokines; Tumor Necrosis Factor-α; Rheumatoid Arthritis; Inflammation

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Lundy, S.K., Sarkar, S., Tesmer, L.A. and Fox, D.A. (2007) Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Research & Therapy, 9, 202. http://dx.doi.org/10.1186/ar2107
[2]	Crotty, S. (2011) Follicular helper CD4 T cells (TFH). Annual Review of Immunology, 29, 621-663. http://dx.doi.org/10.1146/annurev-immunol-031210-101400
[3]	Feldmann, M. and Maini, R.N. (2001) Anti-TNF alpha therapy of rheumatoid arthritis: What have we learned? Annual Review of Immunology, 19, 163-196. http://dx.doi.org/10.1146/annurev.immunol.19.1.163
[4]	de Jong, A.L., Green, D.M., Trial, J.A. and Birdsall, H.H. (1996) Focal effects of mononuclear leukocyte transendothelial migration: TNF-alpha production by migrating monocytes promotes subsequent migration of lymphocytes. Journal of Leukocyte Biology, 60, 129-136.
[5]	Green, D.M., Trial, J. and Birdsall, H.H. (1998) TNFalpha released by comigrating monocytes promotes transendothelial migration of activated lymphocytes. The Journal of Immunology, 161, 2481-2489.
[6]	Rossol, M., Schubert, K., Meusch, U., Schulz, A., Biedermann, B., Grosche, J., Pierer, M., Scholz, R., Baerwald, C., Thiel, A., Hagen, S. and Wagner, U. (2013) Tumor necrosis factor receptor type I expression of CD4+ T cells in rheumatoid arthritis enables them to follow tumor necrosis factor gradients into the rheumatoid synovium. Arthritis & Rheumatism, 65, 1468-1476. http://dx.doi.org/10.1002/art.37927
[7]	Riegsecker, S., Wiczynski, D., Kaplan, M.J. and Ahmed, S. (2013) Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis. Life Sciences, 93, 307-312. http://dx.doi.org/10.1016/j.lfs.2013.07.006
[8]	McInnes, I.B. and Schett, G. (2011) The pathogenesis of rheumatoid arthritis. The New England Journal of Medicine, 365, 2205-2219. http://dx.doi.org/10.1056/NEJMra1004965
[9]	Fox, D.A. (1997) The role of T cells in the immunopathogenesis of rheumatoid arthritis: New perspectives. Arthritis & Rheumatism, 40, 598-609. http://dx.doi.org/10.1002/art.1780400403
[10]	Firestein, G.S. (2003) Evolving concepts of rheumatoid arthritis. Nature, 423, 356-361. http://dx.doi.org/10.1038/nature01661
[11]	Ivashkiv, L.B. (2011) Inflammatory signaling in macrophages: transitions from acute to tolerant and alternative activation states. European Journal of Immunology, 41, 2477-2481. http://dx.doi.org/10.1002/eji.201141783
[12]	Noss, E.H. and Brenner, M.B. (2008) The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis. Immunological Reviews, 223, 252-270. http://dx.doi.org/10.1111/j.1600-065X.2008.00648.x
[13]	Lee, A., Qiao, Y., Grigoriev, G., Chen, J., Park-Min, K.H., Park, S.H., Ivashkiv, L.B. and Kalliolias, G.D. (2013) Tumor necrosis factor alpha induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts. Arthritis & Rheumatism, 65, 928-938. http://dx.doi.org/10.1002/art.37853
[14]	Lam, J., Takeshita, S., Barker, J.E., Kanagawa, O., Ross, F.P. and Teitelbaum, S.L. (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. Journal of Clinical Investigation, 106, 1481-1488. http://dx.doi.org/10.1172/JCI11176
[15]	Abu-Amer, Y., Ross, F.P., Edwards, J. and Teitelbaum, S.L. (1997) Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor. The Journal of Clinical Investigation, 100, 1557-1565. http://dx.doi.org/10.1172/JCI119679
[16]	Kobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., Yasuda, H., Morinaga, T., Higashio, K., Martin, T.J. and Suda, T. (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. The Journal of Experimental Medicine, 191, 275-286. http://dx.doi.org/10.1084/jem.191.2.275
[17]	Smolen, J.S., Han, C., Bala, M., Maini, R.N., Kalden, J.R., van der Heijde, D., Breedveld, F.C., Furst, D.E., Lipsky, P.E. and Group, A.S. (2005) Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: A detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study. Arthritis & Rheumatism, 52, 1020-1030. http://dx.doi.org/10.1002/art.20982
[18]	Binder, N.B., Puchner, A., Niederreiter, B., Hayer, S., Leiss, H., Bluml, S., Kreindl, R., Smolen, J.S. and Redlich, K. (2013) Tumor necrosis factor-inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor-driven model of rheumatoid arthritis. Arthritis & Rheumatism, 65, 608-617. http://dx.doi.org/10.1002/art.37797