title: Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB.
abstract: It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.
authors.affiliation: Department of Cardiology, Affiliated People's Hospital of Jiangsu University, No. 8 DianLi Road, Zhenjiang, Jiangsu, People's Republic of China. ywyao78@sina.com.cn
authors.forename: Yong-wei
authors.initials: YW
authors.lastname: Yao
authors.forename: Guo-hui
authors.initials: GH
authors.lastname: Zhang
authors.forename: Ying-yu
authors.initials: YY
authors.lastname: Zhang
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Li
authors.forename: Cheng-hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Chun-yang
authors.initials: CY
authors.lastname: Yin
authors.forename: Fu-min
authors.initials: FM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B