Inhibition of microglial CD40 expression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10.
Microglia are intrinsic mediators of the central nervous system (CNS) immune response induced by a variety of insults. Activated microglia express costimulatory molecules CD40 and B7 that are important equally for T-cell activation and further activation of microglia. In this study, we sought to investigate the regulation of costimulatory molecule expression on primary microglia and microglial cell line, BV-2, by pituitary adenylyl cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), potent anti-inflammatory neuropeptides. The neuropeptides inhibited CD40 and B7-2 mRNA expression in activated microglia. PACAP decreased surface expression of CD40 and B7-2 on activated microglia. The inclusion of an anti-IL-10 antibody completely abrogated PACAP inhibition of lipopolysaccharide (LPS)-induced CD40 expression, suggesting that PACAP inhibition is at least in part mediated by IL-10. Indeed, PACAP enhanced LPS-induced IL-10 mRNA and protein levels in microglia. These data indicate that PACAP, through an increase in IL-10 protein, can down-regulate important costimulatory molecule expression on microglia, thereby possibly affecting CNS immunity.
Kim
Woong-Ki
WK
Department of Biological Sciences, Rutgers University, 101 Warren Street, Newark, NJ 07102, USA.
Ganea
Doina
D
Jonakait
G Miller
GM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000235:genetics*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497966:Cd86 protein, rat; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D016753:Interleukin-10; D014660:Vasoactive Intestinal Peptide