title: GLP-2 suppresses LPS-induced inflammation in macrophages by inhibiting ERK phosphorylation and NF-κB activation.
abstract: OBJECTIVE
  GLP-2 has been shown to exert anti-inflammatory effects, but the underlying molecular mechanisms remained undefined. As macrophages are important in the development and maintenance of inflammation, we investigated whether exogenous GLP-2 modulates the expression of pro-inflammatory proteins in LPS stimulated murine peritoneal macrophages.
  
  
  METHODS
  Macrophages were pretreated with various concentrations of GLP-2 for 1 h and then stimulated with LPS. The effects on pro-inflammatory enzymes (iNOS and COX-2), and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were analysed by Western blotting, ELISA and qRT-PCR. We also examined whether NF-κB or MAPK signaling was involved in the effects of GLP-2.
  
  
  RESULTS
  In macrophages, GLP-2 blunted the effect of LPS on protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1β and IL-6. Pre-incubation of macrophages with GLP-2 also blunted LPS-induced IκB-α degradation, IκB-α phosphorylation and NF-κB translocation. In the presence of GLP-2, the effect of LPS treatment on ERK phosphorylation was also profoundly blunted. GLP-2 did, however, not significantly modify the effects of LPS on p38 and JNK activities.
  
  
  CONCLUSIONS
  These findings demonstrate that in LPS primed macrophages, GLP-2 reduced pro-inflammatory enzymes and cytokine production via mechanisms involving the suppression of NF-κB activity and ERK phosphorylation.
authors.affiliation: College of Animal Science (Laboratory Animal Center), Jilin University, Changchun, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xie
authors.forename: Bingrun
authors.initials: B
authors.lastname: Liu
authors.forename: Shoupeng
authors.initials: S
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yunhou
authors.initials: Y
authors.lastname: Yin
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Juxiong
authors.initials: J
authors.lastname: Liu
authors.forename: Dianfeng
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D053767:Glucagon-Like Peptide 2; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases