GLP-2 Suppresses LPS-Induced Inflammation in Macrophages by Inhibiting ERK Phosphorylation and NF-kappa B Activation

Background/Aims: 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-alpha, IL-1 beta and IL-6) were analysed by Western blotting, ELISA and qRT-PCR. We also examined whether NF-kappa B or MARK 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-alpha, IL-1 beta and IL-6. Eke-incubation of macrophages with GLP-2 also blunted LPS-induced I kappa B-alpha degradation, I kappa B-alpha phosphorylation and NF-kappa B 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 NE-kappa B activity and ERK phosphorylation. Copyright (C) 2014 S. Karger AG, Basel