Inhibitory effect of extrinsic CO-releasing molecules-2 (CORM-2) on inflammatory responses in mice with LPS-induced acute lung injury / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of extrinsic CO-releasing molecules-2 (CORM-2) on attenuating pulmonary injury and the inflammatory response in LPS-induced acute lung injury of mice.</p><p><b>METHODS</b>Fifty-three mice were assigned to four groups. Mice in sham group (n= 8) underwent sham inhalation, whereas mice in ALI (n= 15) received inhalation of LPS for 30 min, mice in ALI+iCORM (n= 15) underwent LPS inhalation with immediate administration of inactive CORM-2 (8 mg/kg, i.v.), mice in ALI+CORM (n= 15) underwent LPS inhalation with immediate administration of CORM-2 (8 mg/kg, i.v.). PMN accumulation (MPO assay) in mice lungs and TNF-α and IL-1 β in BAL fluid were determined. Activation of NF-kB and expression level of ICAM-1 in the lung were assessed.</p><p><b>RESULT</b>Treatment of ALI mice with CORM-2 attenuated PMN accumulation and prevented activation of NF-kB in the lung. This was accompanied by a decrease of the expression of ICAM-1. In parallel, CORM-2 markedly decreased the production of inflammatory mediators in BAL fluid.</p><p><b>CONCLUSION</b>CORM-2 attenuates the inflammatory response in the lung of LPS-induced ALI by decreasing leukocyte sequestration and interfering with NF-kB activation, expression of ICAM-1 and therefore suppressing endothelial cells pro-adhesive phenotype.</p>