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Article Dans Une Revue International Journal of Experimental Pathology Année : 2007

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

Résumé

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

Domaines

Immunologie

Dates et versions

hal-00318537 , version 1 (04-09-2008)

Identifiants

Citer

Dieudonnée Togbe, Silvia Schnyder-Candrian, Bruno Schnyder, Emilie Doz, Nicolas Noulin, et al.. Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury.. International Journal of Experimental Pathology, 2007, 88 (6), pp.387-91. ⟨10.1111/j.1365-2613.2007.00566.x⟩. ⟨hal-00318537⟩

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