title: GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways.
abstract: The 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.
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. ln657748288@gmail.com.
authors: Nan
authors: N
authors: Li
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. Bowenliucn@outlook.com.
authors: Bo-Wen
authors: BW
authors: Liu
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. rwz1964@163.com.
authors: Wen-Zhi
authors: WZ
authors: Ren
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. juxiong@jlu.edu.cn.
authors: Ju-Xiong
authors: JX
authors: Liu
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. lsnlhh2006@163.com.
authors: Su-Nan
authors: SN
authors: Li
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. shoupengfu@163.com.
authors: Shou-Peng
authors: SP
authors: Fu
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. zengyalong@foxmail.com.
authors: Ya-Long
authors: YL
authors: Zeng
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. xushiyao1989@163.com.
authors: Shi-Yao
authors: SY
authors: Xu
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. yanxuan1992@outlook.com.
authors: Xuan
authors: X
authors: Yan
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. yjgao@jlu.edu.cn.
authors: Ying-Jie
authors: YJ
authors: Gao
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. ccdf@163.com.
authors: Dian-Feng
authors: DF
authors: Liu
authors: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. wang_wei99@jluhp.edu.cn.
authors: Wei
authors: W
authors: Wang
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D015870:Gene Expression; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism* / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System; D017628:Microglia / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D053767:Glucagon-Like Peptide 2; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: MAPK; NF-κB; Parkinson’s disease; glucagon-like peptide-2; microglia