Rheumatoid arthritis chemokine role

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Role of Chemokines During the Different Phases of Rheumatoid Arthritis... 

Quinones MP, Estrada CA, Kalkonde Y, et al. The complex role of the chemokine receptor CCR2 in collagen-induced arthritis implications for therapeutic targeting of CCR2 in rheumatoid arthritis. J Mol Med 2005 83(9) 672-681. 

Nanki T, Hayashida K, El-Gabalawy HS, et al. Stromal cell-derived factor-l-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium. J Immunol 2000 165(11) 6590-6598. 

Blaschke S, Middel P, Domer BG, et al. Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis. Arthritis Rheum 2003 48(7) 1858-1872. 

Another related group of molecules are the chemokines. Chemokines are small peptide molecules that, hke cytokines, were originally associated with the immune system, but which now are recognized as being produced by almost all cells of the body and involved in a multitude of biological functions. Chemokines play many roles, including modulation of the Thl/Th2 balance associated with autoimmunity and hypersensitivity (Montovani et al., 1998), as mediators of allergic inflammation (Bacon and Schall, 1996), and modulation of the function of leukocytes in disease states such as rheumatoid arthritis and asthma. 

The Role of Chemokines in the Pathogenesis of Rheumatoid Arthritis and Possible Connections with RRV and EPA... 

Chemokines regulate the migration of cells in vivo and dysregulated expression of chemokines and their receptors are implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. In this review, we describe the use of several methods to study the role of chemoattractant receptors, including chemokine receptors, on the recruitment of neutrophils into the joint in the K/BxN model of inflammatory arthritis. This includes both traditional methods, such as flow cytometry, immunohistochemistry, and enzyme assays, as well as multiphoton in vivo microscopy that we have adapted to study the role of immune cell trafficking in and around the joint in live mice. 

These data demonstrate the involvement of chemokines and their receptors in inflammatory joint disease. Further information on the role of chemokines and chemokine receptors should come from the use of transgenic or knockout mice in animal models of arthritis. It is clear that blocking the interactions between chemokines and their receptors using antichemokine, antichemokine receptor monoclonal antibodies, or chemokine receptor antagonists may prove to be of therapeutic value in the control inflammatory diseases such as rheumatoid arthritis. 

Part II of the book explores the role of chemokines in a variety of chronic and acute inflammatory diseases, including acute respiratory distress syndrome (ARDS), asthma, interstitial lung disease, rheumatoid arthritis, and organ transplant rejection. These topics are discussed through a presentation of the pathogenesis of the disease, using a wide range of clinically relevant animal models of the disease, as well as the examination of chemokine expression in clinical samples. 

Blaschke, S., Middel, P., Dorner, B. G., Blaschke, V., Hummel, K. M., Kroczek, R. A., Reich, K., Benoehr, P., Koziolek, M., and Muller, G. A. (2003a). Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis. Arthritis Rheum. 48, 1858-1872. 

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