Ethanol selectively modulates inflammatory activation signaling of brain microglia.
In spite of well-known deleterious effects of alcohol on the nervous system in general, its specific effect on the brain immune system remains poorly understood. In order to better understand the effect of alcohol consumption on the innate immunity and inflammatory responses in the central nervous system (CNS), we sought to determine how ethanol influences inflammatory activation of microglia that function as the resident immune defense system of the brain. After treatment of BV-2 mouse microglial cells or rat primary microglia cultures with various stimuli, nitric oxide (NO) production was measured as an indicator of microglial activation. Pretreatment of the cells with ethanol (10-100 mM) for 1 h resulted in a significant decrease in lipopolysaccharide (LPS)-induced, but not interferon-gamma (IFNgamma)-induced, NO production, indicating that ethanol specifically inhibits LPS-induced inflammatory activation of microglia. This was further supported by the ethanol inhibition of LPS-induced IL-1beta expression. In addition, ethanol pretreatment selectively regulated LPS-induced NF-kappaB signaling pathway without affecting IFNgamma-induced signal transducer and activator of transcription 1 (STAT1) phosphorylation, interferon regulatory factor-1 (IRF-1) induction or IFNgamma-inducible IP-10 expression. The modulation of LPS-induced NF-kappaB by ethanol was due to the inhibition of coactivator p300. Altogether, these results suggest that acute ethanol exposure may selectively modulate signal transduction pathways associated with inflammatory activation of microglia, which may lead to derangement of CNS immune and inflammatory responses.
Lee
Heasuk
H
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, #101 Dong-In, Joong-gu, Daegu 700-422, Republic of Korea.
Jeong
Jaeyoon
J
Son
Eunyung
E
Mosa
Ahmed
A
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Ha
Jeoung-Hee
JH
Kim
In Kyeom
IK
Lee
Maan Gee
MG
Kim
Choong-Young
CY
Suk
Kyoungho
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D000431:Ethanol / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D000431:Ethanol; D007371:Interferon-gamma