Role of nitric oxide in regulating secreted phospholipase A2 release from astrocytes.
Inflammatory stimuli such as lipopolysaccharide increase nitric oxide and secreted phospholipase A2 release from glial cells. However, the signaling mechanism(s) regulating secreted phospholipase A2 in glial cells is not known. Here, rat brain astrocytes treated with lipopolysaccharide generated nitrite and released secreted phospholipase A2, while microglia generated nitrite without releasing secreted phospholipase A2. Unexpectedly, attenuation of nitrite production by pretreatment with the nitric oxide synthase inhibitor N-Omega-nitro-L-arginine methyl ester greatly enhanced lipopolysaccharide-stimulated secreted phospholipase A2 release from astrocytes; postreatment with N-Omega-nitro-L-arginine methyl ester did not potentiate secreted phospholipase A2 release, and addition of an nitric oxide donor attenuated the secreted phospholipase A2 release. The regulation of secreted phospholipase A2 may act via the transcription factor nuclear factor-kappaB, as a nuclear factor-kappaB inhibitor attenuated lipopolysaccharide-stimulated secreted phospholipase A2 release. These results demonstrate the role of basal nitric oxide levels as a regulator of inflammatory secreted phospholipase A2 release from glial cells of the brain.
Wang
Guansong
G
Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA.
Daniel
Bron M
BM
DeCoster
Mark A
MA
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002109:Caffeic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002614:Chelating Agents / Q000494:pharmacology; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002109:Caffeic Acids; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide; D004492:Edetic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D019331:NG-Nitroarginine Methyl Ester