Carbon monoxide attenuates lipopolysaccharide-induced lung injury by mitofusin proteins via p38 MAPK pathway

Background The protective effects of carbon monoxide against the lipopolysaccharide (LPS)-induced lung injury were attributed to maintenance of mitochondrial dynamics, but the mechanisms remain unexplored. Materials and methods Using a rat model of acute lung injury induced by LPS and the LPS attacking cell model, we investigated the effects of pretreatment of carbon monoxide molecule-2 (CORM-2) on the acute lung injury and expressions of mitofusin proteins that play a critical role in mitochondrial dynamics. Results We found that preadministration of CORM-2, not the inactive form of CORM-2, significantly reduced the lung injury, levels of inflammatory cytokines, and the degree of oxidative stress caused by LPS. What was more, it increased the expressions of mitofusin proteins. Similar findings were also found in LPS-stimulating cell model. However, when the cells were treated in combination with LPS, CORM-2, and SB203580, it completely abolished the protection of CORM-2, reflected by increased levels of inflammatory cytokines and malonaldehyde, decreased activities of superoxide dismutase, along with the lower expressions of mitofusin proteins and the ratio of p-p38 mitogen activated protein kinase to p38 mitogen activated protein kinase. Conclusions Our observations suggest that pretreatment with CORM-2 could attenuate LPS-induced lung injury by inducing the expressions of mitofusin proteins via p38 mitogen activated protein kinase pathway.