title: Ischemic preconditioning and lipopolysaccharide attenuate nuclear factor-kappaB activation and gene expression of inflammatory cytokines in the ischemia-reperfused rat heart.
abstract: Ischemic preconditioning (IP) and pretreatment with lipopolysaccharide (LPS) reduce myocardial infarct size, but the precise mechanisms remain unknown. Rats were divided into 3 groups: the Control (C) group was subjected to 30 min ischemia followed by 3 h reperfusion; the IP and LPS groups had the same ischemia-reperfusion (I-R) insult with either preconditioning stimuli or pretreatment with LPS, respectively. Infarct size was smaller in the IP (23.4+/-2.3% of risk zone size) and LPS groups (28.5+/-2.0% of risk zone size) than in the C group (52.3+/-3.4% of risk zone size). Nuclear factor kappa-B (NF-kappaB) binding activity increased at 30 min reperfusion and declined thereafter, then rose again at 3 h reperfusion in the C group. The values in the IP (362% of control) and LPS (324% of control) groups were higher before I-R, and then decreased from 30 min (46% and 64% of control, respectively) until 3 h reperfusion (22% and 36% of control, respectively). Nuclear staining of NF-kappaB after reperfusion was less in the IP and LPS groups than in the C group. Expressions of cytokine mRNAs (interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha) were detected 30 min after the onset of reperfusion and their levels remained high after 3 h of reperfusion. These expressions of cytokine mRNAs after I-R were substantially suppressed by IP and LPS, although IP and LPS alone induced modest expressions of these cytokine mRNAs. These data suggest that IP and LPS contribute to infarct size reduction via the downregulation of NF-kappaB and the attenuation of cytokine gene expression.
authors.affiliation: The Second Department of Internal Medicine, Ehime University School of Medicine, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Hiasa
authors.forename: M
authors.initials: M
authors.lastname: Hamada
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Hiwada
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger