TLR4-MD2 signaling pathway induced by endotoxin / 中国药理学通报

ABSTRACT

Recent evidence suggests Toll like receptor 4 (TLR4) and its accessory protein MD2 mediate endotoxin/lipopolysaccharide (LPS) signaling. LPS binds to LPS binding protein (LBP) in plasma and is delivered to CD14. Next, LPS is transferred to TLR4 MD2 complex. LPS activates several intracellular signaling pathways that include the NF ?B pathway and three mitogen activated peotein kinase (MAPK) pathway: extracellular signal regulated kinase (ERK), c Jun N terminal kinase (JNK) and p38. These signaling pathways in turn activate NF ?B and AP 1 (c fos/c jun), which coordinate the induction of many genes encoding inflammatory mediators. Targeting the signaling molecule in the pathway will develop new remedies for treatment of inflammatory disorder.