Glucagon-like peptide-1 inhibits LPS-induced IL-1beta production in cultured rat astrocytes

Neurosci Res. 2006 Aug;55(4):352-60. doi: 10.1016/j.neures.2006.04.008. Epub 2006 May 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Brain / immunology
  • Brain / metabolism*
  • Brain / physiopathology
  • Cell Shape / drug effects
  • Cell Shape / physiology
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Encephalitis / immunology
  • Encephalitis / metabolism*
  • Encephalitis / physiopathology
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide-1 Receptor
  • Inflammation Mediators / pharmacology
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Microglia / drug effects
  • Microglia / immunology
  • Microglia / metabolism*
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Glucagon / drug effects
  • Receptors, Glucagon / metabolism
  • Up-Regulation / drug effects

Substances

  • Adenylyl Cyclase Inhibitors
  • Cyclic AMP Response Element-Binding Protein
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Inflammation Mediators
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Cyclic AMP
  • Adenylyl Cyclases