GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways
AbstractThe pathogenesis of Parkinson’s disease (PD) often involves the over-activation of microglia. Over-activated microglia could produce several inflammatory mediators, which trigger excessive inflammation and ultimately cause dopaminergic neuron damage. Anti-inflammatory effects of glucagon-like peptide-2 (GLP-2) in the periphery have been shown. Nonetheless, it has not been illustrated in the brain. Thus, in this study, we aimed to understand the role of GLP-2 in microglia activation and to elucidate the underlying mechanisms. BV-2 cells were pretreated with GLP-2 and then stimulated by lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory enzymes (iNOS and COX-2) and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α); the related signaling pathways were evaluated by Western blotting. The rescue effect of GLP-2 on microglia-mediated neurotoxicity was also examined. The results showed that GLP-2 significantly reduced LPS-induced production of inducible nitric oxide synthase (iNOS), cyclooxygenase-s (COX-2), IL-1β, IL-6 and TNF-α. Blocking of Gαs by NF449 resulted in a loss of this anti-inflammatory effect in BV-2 cells. Analyses in signaling pathways demonstrated that GLP-2 reduced LPS-induced phosphorylation of ERK1/2, JNK1/2 and p65, while no effect was observed on p38 phosphorylation. In addition, GLP-2 could suppress microglia-mediated neurotoxicity. All results imply that GLP-2 inhibits LPS-induced microglia activation by collectively regulating ERK1/2, JNK1/2 and p65. View Full-Text
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Li, N.; Liu, B.-W.; Ren, W.-Z.; Liu, J.-X.; Li, S.-N.; Fu, S.-P.; Zeng, Y.-L.; Xu, S.-Y.; Yan, X.; Gao, Y.-J.; Liu, D.-F.; Wang, W. GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways. Int. J. Mol. Sci. 2016, 17, 190.
Li N, Liu B-W, Ren W-Z, Liu J-X, Li S-N, Fu S-P, Zeng Y-L, Xu S-Y, Yan X, Gao Y-J, Liu D-F, Wang W. GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways. International Journal of Molecular Sciences. 2016; 17(2):190.Chicago/Turabian Style
Li, Nan; Liu, Bo-Wen; Ren, Wen-Zhi; Liu, Ju-Xiong; Li, Su-Nan; Fu, Shou-Peng; Zeng, Ya-Long; Xu, Shi-Yao; Yan, Xuan; Gao, Ying-Jie; Liu, Dian-Feng; Wang, Wei. 2016. "GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways." Int. J. Mol. Sci. 17, no. 2: 190.
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