Heme oxygenase-1 mediates the anti-inflammatory effects of acute alcohol on IL-10 induction involving p38 MAPK activation in monocytes
Authors
Drechsler, YvonneDolganiuc, Angela
Norkina, Oxana
Romics, Laszlo
Li, Weibo
Kodys, Karen
Bach, Fritz H.
Mandrekar, Pranoti
Szabo, Gyongyi
UMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDocument Type
Journal ArticlePublication Date
2006-08-05Keywords
AnimalsAnti-Inflammatory Agents, Non-Steroidal
Cells, Cultured
Enzyme Activation
Ethanol
Female
Heme Oxygenase-1
Humans
Interleukin-10
Mice
Mice, Inbred C57BL
Monocytes
p38 Mitogen-Activated Protein Kinases
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Inflammation and immunoregulatory cytokines play a central role in alcohol-induced liver damage. We previously reported that acute alcohol treatment augments IL-10 and inhibits TNF-alpha production in monocytes. Heme oxygenase-1 (HO-1), a stress-inducible protein, also regulates IL-10 and TNF-alpha production. Here, we report that augmentation of LPS-induced IL-10 production by alcohol was prevented by inhibition of HO-1 activity. Acute ethanol increased LPS-induced enzyme activity and RNA levels of HO-1, and DNA binding of AP-1, a transcription factor essential in HO-1 regulation. LPS-induced phospho-p38 MAPK levels were augmented by ethanol treatment and the p38 inhibitor, SB203580, prevented both the ethanol-induced increase in IL-10 production and the inhibitory effect of ethanol on TNF-alpha production. Ethanol-induced down-regulation of TNF-alpha production was abrogated by inhibition of HO-1. We found that LPS-induced activation of NF-kappaB, a regulator of TNF-alpha, was inhibited by both ethanol treatment and HO-1 activation, but the ethanol-induced inhibition of NF-kappaB was HO-1 independent. In LPS-challenged mice in vivo, both acute alcohol administration and HO-1 activation augmented IL-10 and inhibited TNF-alpha serum levels. These results show that 1) acute alcohol augments HO-1 activation in monocytes, 2) HO-1 activation plays a role in alcohol-induced augmentation of IL-10 production likely via increased p38 MAPK activation, and 3) HO-1 activation is involved in attenuation of TNF-alpha production by alcohol independent of inhibition of NF-kappaB activation by alcohol. Thus, HO-1 activation is a key mediator of the anti-inflammatory effects of acute alcohol on monocytes.Source
J Immunol. 2006 Aug 15;177(4):2592-600.
DOI
10.4049/jimmunol.177.4.2592Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38204PubMed ID
16888021Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.177.4.2592