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.

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

“…Importantly, the addition of PfHz caused further enhancement of NF-κB translocation into the nucleus, with peak expression at 8 h under physiological (37°C) and heat-shock conditions (42°C, Figures 4A and B). Consistent with the fact that heat-shock treatment increases Hsp70 and thereby reduces NF-κB translocation into the nucleus (20)(21)(22), the effect of PfHz on NF-κB at 42°C was not as pronounced as that observed at 37°C (Figures 4A and B). the time-dependent effect of PfHz on protein levels was determined.…”

“…Circulating Aberrant NF-κB activation has been associated with overabundant inflammatory events in arthritis, asthma, ischemia, septic shock and other autoimmune and inflammatory diseases (19,20). Persistent inhibition of NF-κB activation has been linked to apoptosis, inappropriate immune cell development and delayed cell growth (19).…”

“…Persistent inhibition of NF-κB activation has been linked to apoptosis, inappropriate immune cell development and delayed cell growth (19). Overexpression of Hsp70 in in vitro models inhibits nuclear translocation of NF-κB by preventing degradation of IκB, thereby reducing the elevated production of proinflammatory mediators (20)(21)(22). Based on these studies and our transcriptomics experiment, we investigated the role of Hsp70 in modulating NF-κB and Hsp70 in malaria clinical outcomes.…”

The effect of hydroxy safflower yellow A on inflammatory reaction in myocardium of the rats after acute myocardial infarction

“…It can be activated by a variety of different stimuli and it participates in expression and regulation of a variety of genes, especially genes involved in defense functions of the body. In recent years, studies have shown that myocardial ischemia at early stage can induce activation of NF-κB to regulate gene transcription (Xiyuan et al, 2009) and NF-κB plays an important role in myocardial ischemic preconditioning, ischemia, hypoxia, reperfusion injury and apoptosis, especially in the process of inducing myocardial inflammatory reaction, and increasing the release of TNF-α, IL-1β and IL-6 (Lu et al, 2009;Yao et al, 2011), and aggravating myocardial injury. At present, a variety of NF-κB inhibitors have been used to relieve myocardial ischemia and reperfusion injury.…”

The Effect of Silver Carp Skin-Derived Peptides on the Activities of VEGF and Hsp70.1 Gene Transcription Promoters

“…Both increased production of heat shock proteins and their active participation in the process of wound healing have been demonstrated over a period of approximately two to ten hours after the damage [23,24]. It is known that increased production of hsp70 protein may occur in the case of tissue damage that is caused both by internal tissue factors, such as PHSRN peptide derived from fibronectin [25], and bacterial lipopolysaccharides [26], where hsp70 expression inhibits cytokine excretion induced by lipopolysaccharides; this increases the survival rate of (for example) rats injected with lipopolysaccharides [27].…”