Signal transduction by the lipopolysaccharide receptor, Toll‐like receptor‐4
Tóm tắt
An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS – Toll‐like receptor 4 (TLR4) – but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD‐2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88‐like adapter (Mal), leads to the activation of nuclear factor‐κB (NF‐κB). A later response to LPS makes use of TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF) and TRIF‐related adapter molecule (TRAM), and leads to the late activation of NF‐κB and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS.
Từ khóa
Tài liệu tham khảo
Haziot A, 1998, The induction of acute phase proteins by lipopolysaccharide uses a novel pathway that is CD14‐independent, J Immunol, 160, 2570, 10.4049/jimmunol.160.6.2570
Dunne A, 2003, The interleukin‐1 receptor/Toll‐like receptor superfamily: signal transduction during inflammation and host defense, Sci STKE, 171
Kuno K, 1993, Structure and function of the intracellular portion of the mouse interleukin 1 receptor (type I). Determining the essential region for transducing signals to activate the interleukin 8 gene, J Biol Chem, 268, 13510, 10.1016/S0021-9258(19)38679-X
De Weers M, 1994, B‐cell antigen receptor stimulation activates the human Bruton's tyrosine kinase, which is deficient in X‐linked agammaglobulinemia, J Biol Chem, 269, 23857, 10.1016/S0021-9258(19)51014-6
Haziot A, 1995, CD14‐deficient mice are exquisitely insensitive to the effects of LPS, Prog Clin Biol Res, 392, 349