TLR4 signaling-induced heme oxygenase upregulation in the acute lung injury: role in hemorrhagic shock and two-hit induced lung inflammation.
Resuscitated hemorrhagic shock is believed to promote the development of acute lung injury (ALI) by priming the immune system for an exaggerated inflammatory response to a second trivial stimulus. This work explored effects of TLR4 on hemorrhage-induced ALI and "second-hit" responses, and further explore the mechanisms involved in "second-hit" responses. Expression of HO-1, IL-10, lung W/D and MPO markedly increased at nearly all time-points examined in HSR/LPS group as compared with sham/LPS group in WT mice. In HSR/LPS mice, the induced amount of IL-10 and the expressions of HO-1 of WT mice were significantly higher compared with TLR-4d/d. This study provides in vivo evidence that pulmonary infections after LPS instillation contribute to local tissue release of pro-inflammatory mediators after HSR systemic. Activation of TLR4 might induce HO-1 expression and HO-1 modulates proinflammatory responses that are triggered via TLR4 signaling.
Department of Anesthesiology, Zhongnan Hospital, Medical College of Wuhan University, Donghu Road, Wuhan, 430071, Hubei, People's Republic of China.
Chang
C
Chen
Fan
F
Zhang
Zongze
Z
Zhang
Mian
M
Peng
Yanlin
Y
Wang
Yingying
Y
Chen
D055371:Acute Lung Injury / Q000201:enzymology* / Q000276:immunology; D000818:Animals; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008933:Mitochondrial Swelling; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D008565:Membrane Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse