Chemokines and Chemokine Receptors as Novel Therapeutic Targets in Rheumatoid Arthritis (RA):Inhibit

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Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation ofleukocytes at inflammatory sites.Over the past decade,accumulating evidence indicated a crucial role forchemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis(RA).RA is a chronicautoimmune disease in which the synovial tissue is heavily infiltrated by leukocytes.Chemokines play animportant role in the infiltration,localization,retention of infiltrating leukocytes and generation of ectopicgerminal centers in the inflamed synovium.Recent evidence also suggests that identification of inhibitorsdirectly targeting chemokines or their receptors may provide a novel therapeutic strategy in RA.TraditionalChinese medicines(TCMs) have a long history in the treatment of inflammatory joint disease.The basis for theclinical benefits of TCM remains largely unclear.Our studies have led to the identification of numerous novelchemokine/chemokine receptor inhibitors present in anti-inflammatory TCMs.All of these inhibitors werepreviously reported by other researchers to have anti-arthritic effect,which may be attributable,at least inpart,to their inhibitory effect on chemokine and/or chemokine receptor.Therefore,identification of agentscapable of targeting chemokine/chemokine receptor interactions has suggested a mechanism of action forseveral TCM components and provided a means of identifying additional anti-RA TCM.Thus,this approachmay lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treatdiseases associated with inappropriately overactive chemokine mediated inflammatory reactions.Cellular &Molecular Immunology.2004;1(5):336-342. Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory sites. Over the past decade, accumulating evidence indicated a crucial role for chemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis (RA). RA is a chronic autoimmune disease in which the synovial tissue is heavily infiltrated by leukocytes. Chemokines play animportant role in the infiltration, localization, retention of infiltrating leukocytes and generation of ectopic germinal sites in the inflamed synovium. Provence also suggests that identification of inhibitors directly targeted chemokines or their receptors may provide a novel therapeutic strategy in RA. Traditional Chinese medicines (TCMs) have a long history in the treatment of inflammatory joint disease. The basis for the clinical benefits of TCM remains largely unclear. Our studies have led to the identification of novel novelchemokine / chemokine receptor inhibitors presen t in anti-inflammatory TCMs. All of these inhibitors werepreviously reported by other researchers to have anti-arthritic effect, which may be attributable, at least inpart, to their inhibitory effect on chemokine and / or chemokine receptor.Therefore, identification of agentscapable of targeting chemokine / chemokine receptor interactions has suggested a mechanism of action forseveral TCM components and provided a means of identifying additional anti-RA TCM .hus, this approachmay lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treatdiseases associated with inappropriate overactive chemokine mediated inflammatory reactions. Cellular & Molecular Immunology. 2004; 1 (5): 336-342.
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