Effect of carbon monoxide-releasing molecules II-liberated CO on suppressing inflammatory response in sepsis by interfering with nuclear factor kappa B activation.

Abstract

Sepsis continues to be a challenge in clinic. The rates of mortality in sepsis patients remain high. The present study aimed to investigate the effects and the underlying mechanisms of carbon monoxide-releasing molecules II (CORM-2)-liberated CO on suppressing inflammatory response in sepsis. It was shown that treatment of septic mice with CORM-2 attenuated PMN accumulation, downregulated cytokines production, inhibited expressions of iNOS and NF-κB activity in the lung and liver. In parallel, CORM-2 prevented activation of NF-κB in LPS-stimulated HUVEC. This was accompanied by a decrease in ROS and NO production, expression of ICAM-1 and subsequent PMN adhesion to HUVEC. These findings demonstrated that CORM-released CO attenuates inflammatory responses by interfering with NF-κB activation and therefore decreasing the expression of ICAM-1 and NO production, attenuating the oxidative stress and inflammation in sepsis.