Ischemic preconditioning and lipopolysaccharide attenuate nuclear factor-kappa B activation and gene expression of inflammatory cytokines in the ischemia-reperfused rat heart

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 3 0 min ischemia followed by 3 h reperfusion; the IP and LPS groups had the s ame ischernia-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 ruin reperfusion and d eclined thereafter, then rose again at 3h reperfusion in the C group. The v alues in the IP (362% of control) and LPS (324% of control) groups were hig her before I-R, and then decreased from 30 min (46% and 64% of control, res pectively) until 3h reperfusion (22% and 36% of control, respectively). Nuc lear staining of NF-kappaB after reperfusion was less in the IP and LPS gro ups than in the C group. Expressions of cytokine mRNAs (interleukin-1 beta, 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 reperf usion. These expressions of cytokine mRNAs after I-R were substantially sup pressed 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 attenuat ion of cytokine gene expression.