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Stimulation of alpha7 nicotinic acetylcholine receptor by nicotine attenuates inflammatory response in macrophages and improves survival in experimental model of sepsis through heme oxygenase-1 induction.
MedLine Citation:
PMID:  21083424     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Abstract Activation of nicotinic acetylcholine receptor alpha7 subunit (α7nAChR) by nicotine leads to the improved survival rate in experimental model of sepsis. Previously, we demonstrated that heme oxygenase (HO)-1 inducers or carbon monoxide significantly increased survival of lipopolysaccharide (LPS)-induced and cecal ligation and puncture-induced septic mice by reduction of high mobility group box 1 release, a late mediator of sepsis. However, that activation of α7nAChR by nicotine provides anti-inflammatory action through HO-1 upregulation has not been elucidated. Here we show that HO-1-inducible effect by nicotine was mediated through sequential event-Ca(2+) influx, classical protein kinase C activation, and reactive oxygen species production-which activates phosphoinositol-3-kinase/Akt/Nrf-2 pathway. In addition, HO-1 is required for nicotine-mediated suppression of tumor necrosis factor-α, inducible nitric oxide synthase, and high mobility group box 1 expression induced by LPS in macrophages, as evidenced by the fact that nicotine failed to inhibit production of these mediators when HO-1 was suppressed. Importantly, nicotine-induced survival rate was reduced by inhibition of HO-1 in LPS- and cecal ligation and puncture-treated septic mice. Collectively, these data suggest that activation of α7nAChR by nicotine is critical in the regulation of anti-inflammatory process, which could be mediated through HO-1 expression. Thus, we conclude that activation of α7nAChR by nicotine provides anti-inflammatory action through HO-1 upregulation. Antioxid. Redox Signal. 14, 2057-2070.
Authors:
Konstantin Tsoyi; Hwa Jin Jang; Jong Woo Kim; Hong Kyung Chang; Young Soo Lee; Hyun-Ock Pae; Hye Jung Kim; Han Geuk Seo; Jae Heun Lee; Hun-Taeg Chung; Ki Churl Chang
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Publication Detail:
Type:  Journal Article     Date:  2011-03-17
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  14     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2057-70     Citation Subset:  IM    
Affiliation:
1 Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University , Jinju, Korea.
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