Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury.

摘要: Recent studies on endotoxin/lipopolysaccharide (LPS)-induced acute inflammatory response in the lung are reviewed. The airway to inhaled endotoxin is mediated through Toll-like receptor 4 (TLR4) and CD14 signalling as mice deficient for TLR4 or unresponsive endotoxin. Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)-12 keratinocyte-derived chemokine (KC) production, protein leak neutrophil recruitment abrogated adaptor molecules myeloid differentiation 88 (MyD88) Toll/Interleukin-1 (TIR)-domain-containing (TIRAP), but independent of TIR-domain-containing adaptor-inducing interferon-beta (TRIF). In particular, LPS-induced TNF required dispensable cell recruitment. Lipopolysaccharide induces activation p38 mitogen-activated kinase (MAPK). Inhibition pulmonary MAPK activity abrogates into lungs broncho-alveolar space. conclusion, TLR4-mediated, bronchoconstriction pathology dependent TLR4/CD14/MD2 expression using adapter proteins TIRAP MyD88, while TRIF, IL-1R1 IL-18R pathways dispensable. Further downstream this axis signalling, blockade reduces only inhibition completely endotoxin-induced inflammation.