Glucagon-like peptide-1 inhibits LPS-induced IL-1beta production in cultured rat astrocytes.
Glia play an important role in neurotoxicity in neurodegenerative diseases. In this study, we investigated the expression of glucagon-like peptide-1 (GLP-1) and its receptor, and the effects of GLP-1 on lipopolysaccharide (LPS)-induced IL-1beta mRNA expression and IL-1beta production in glia. GLP-1-like immunoreactivity was observed in amoeboid microglia, but not ramified microglia or astrocytes. GLP-1 binding and GLP-1 receptor mRNA expression were observed in both astrocytes and microglia. GLP-1-induced morphological changes in microglia from the ramified type to the amoeboid type, suggesting an increase in production and release of endogenous GLP-1. GLP-1 prevented the LPS-induced IL-1beta mRNA expression, which effect was, in turn, inhibited by pretreatment with SQ22536, an adenylate cyclase inhibitor. GLP-1 also increased cAMP concentration and cAMP response element-binding protein phosphorylation in astrocytes. These results suggest that GLP-1 may be a modulator of inflammation in the central nervous system.
Iwai
Takashi
T
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Ito
Satoshi
S
Tanimitsu
Kahori
K
Udagawa
Shunichi
S
Oka
Jun-Ichiro
J
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D017362:Cyclic AMP Response Element-Binding Protein; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D000262:Adenylyl Cyclases