title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Peng
authors.forename: Yinggang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kevin
authors.initials: K
authors.lastname: Wilhelmsen
authors.forename: Chenfei
authors.initials: C
authors.lastname: Jia
authors.forename: Jue
authors.initials: J
authors.lastname: Jin
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Xue
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Feng
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Buwei
authors.initials: B
authors.lastname: Yu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D002432:Cecum; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008026:Ligation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis* / Q000235:genetics; D011677:Punctures; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054439:Ghrelin; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012333:RNA, Messenger