Abstract:
BACKGROUND:Many studies have shown that ghrelin can down-regulate inflammatory cytokine expression via the inhibition of NF-κB 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-κB 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 6h after CLP or sham operation and analyzed for lung histopathology, neutrophil infiltration, inflammatory cytokines (TNF-α, and IL-6), NOD2 mRNA expression, and activation of NF-κB. Furthermore, survival was recorded for ten days in additional groups of rats. RESULTS:Compared with sham group, neutrophil infiltration, TNF-α and IL-6 levels, NOD2 mRNA expression, as well as NF-κB activation in lungs from rats undergoing CLP 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 CLP 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-κB.
journal_name
Int Immunopharmacoljournal_title
International immunopharmacologyauthors
Peng Z,Zhu Y,Zhang Y,Wilhelmsen K,Jia C,Jin J,Xue Q,Feng X,Zhang F,Yu Bdoi
10.1016/j.intimp.2012.04.006subject
Has Abstractpub_date
2012-08-01 00:00:00pages
440-5issue
4eissn
1567-5769issn
1878-1705pii
S1567-5769(12)00105-1journal_volume
13pub_type
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