| First Author | Tsoyi K | Year | 2011 |
| Journal | Antioxid Redox Signal | Volume | 14 |
| Issue | 11 | Pages | 2057-70 |
| PubMed ID | 21083424 | Mgi Jnum | J:359380 |
| Mgi Id | MGI:7787314 | Doi | 10.1089/ars.2010.3555 |
| Citation | Tsoyi K, et al. (2011) 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. Antioxid Redox Signal 14(11):2057-70 |
| abstractText | Activation of nicotinic acetylcholine receptor alpha7 subunit (alpha7nAChR) 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 alpha7nAChR 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-alpha, 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 alpha7nAChR 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 alpha7nAChR by nicotine provides anti-inflammatory action through HO-1 upregulation. |
