tailieunhanh - Báo cáo y học: "The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài:The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells. | Available online http content 8 2 205 Review The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells Francis Dodeller and Hendrik Schulze-Koops Nikolaus Fiebiger Center for Molecular Medicine Clinical Research Group III and Department of Internal Medicine III University of Erlangen-Nuremberg Glueckstrasse 6 91054 Erlangen Germany Corresponding author Hendrik Schulze-Koops schulze-koops@ Published 17 February 2006 This article is online at http content 8 2 205 2006 BioMed Central Ltd Arthritis Research Therapy 2006 8 205 doi ar1905 Abstract Since the identification of the p38 mitogen-activated protein kinase MAPK as a key signal-transducing molecule in the expression of the proinflammatory cytokine tumor necrosis factor TNF more than 10 years ago huge efforts have been made to develop inhibitors of p38 MAPK with the intent to modulate unwanted TNF activity in diseases such as autoimmune diseases or sepsis. However despite some anti-inflammatory effects in animal models no p38 MAPK inhibitor has yet demonstrated clinical efficacy in human autoimmune disorders. One possible reason for this paradox might relate to the fact that the p38 MAPK signaling cascade is involved in the functional regulation of several different cell types that all contribute to the complex pathogenesis of human autoimmune diseases. In particular p38 MAPK has a multifaceted role in CD4 T cells that have been implicated in initiating and driving sustained inflammation in autoimmune diseases such as rheumatoid arthritis or systemic vasculitis. Here we review recent advances in the understanding of the role of the p38 MAPK signaling cascade in CD4 T cells and the consequences that its inhibition provokes in T cell functions in vitro and in vivo. These new data suggest that p38 MAPK inhibitors may elicit several unwanted effects in human autoimmune diseases but may be useful for the treatment of allergic