Effects of ghrelin on pulmonary NOD2 mRNA expression and NF-κB activation when protects against acute lung injury in rats challenged with cecal ligation and puncture

Background: Many studies have shown that ghrelin can down-regulate inflammatory cytokine expression via the inhibition of NF-kappa B activity and therefore, its administration to septic patients is considered beneficial. However, our knowledge of ghrelin's effects on the upstream activators of the NF-kappa B pathway, such as NOD2, is still limited. This study aimed to investigate the possible involvement of the NOD2 signaling pathway in the anti-inflammatory effects of ghrelin. Methods: Twenty-four male SD rats received cecal ligation and puncture (CLP) or sham operation, followed by infusion of saline or ghrelin. The lungs were harvested 6 h after CLP or sham operation and analyzed for lung histopathology, neutrophil infiltration, inflammatory cytokines (TNF-alpha, and IL-6), NOD2 mRNA expression, and activation of NF-kappa B. Furthermore, survival was recorded for ten days in additional groups of rats. Results: Compared with sham group, neutrophil infiltration, TNF-alpha and IL-6 levels, NOD2 mRNA expression, as well as NF-kappa B activation in lungs from rats undergoing CU' were significantly increased. After the administration of ghrelin, all inflammatory parameters analyzed were lower than those without ghrelin following CLP. In addition, ghrelin improved survival after CLP. Conclusion: Our results indicate that in a CU' model of sepsis, the beneficial effects that ghrelin has on inflammatory outcomes are mediated at least in part through inhibition of NOD2 expression upstream of NF-kappa B. (C) 2012 Elsevier B.V. All rights reserved.