Selective modulation of microglial signal transduction by PACAP.
We have investigated the possible effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on signal transduction pathways associated with inflammatory activation of BV-2 mouse microglia cells. Pretreatment of the cells with PACAP resulted in a significant decrease in LPS- or IFNgamma-induced NO production as well as iNOS and IL-1beta mRNA levels. The inhibitory effect of PACAP appeared to be mediated through an increase in intracellular cAMP. PACAP inhibition of LPS-induced NO production was accompanied by inhibition of p38 MAPK activation, but not ERK, JNK, or NF-kappaB. IFNgamma-induced STAT-1 activation or IRF-1 induction was not significantly influenced by PACAP. Therefore, PACAP appears to suppress inflammatory activation of BV-2 microglia via specific inhibition of LPS-induced p38 MAPK pathway.
Lee
Heasuk
H
Department of Pharmacology, School of Medicine, Kyungpook National University, #101 Dong-In, Joong-gu, Daegu, 700-422 Korea.
Suk
Kyoungho
K
D000818:Animals; D002461:Cell Line, Transformed; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
C495402:Adcyap1 protein, mouse; D008070:Lipopolysaccharides; D009479:Neuropeptides; D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases