Evidence of multi-step regulation of HSP72 expression in experimental sepsis

Heat shock proteins (Hsps) are a family of highly conserved proteins induce d in response to various stresses. Hsps protect cells against subsequent le thal circumstances. Previous work from our laboratory has indicated that Hs p72 is not induced during experimental sepsis in rats, but the regulation o f the induction of Hsp72 synthesis in this disease cascade has not been inv estigated. In the present study, we evaluated the expression of the hsp72 g ene, focusing on the activation and DNA-binding ability of heat shock facto r 1 (HSF1), hsp mRNA accumulation, and Hsp72 synthesis in animal sepsis mod els induced by cecal ligation and puncture procedure. The results were comp ared with those of sham-treated and heat-shocked rats. It was shown that th e expression of the hsp72 gene in sepsis was a multi-step process, as previ ously documented in in vitro studies. Hsp72 synthesis was not induced durin g sepsis, whereas DNA binding of HSF was detectable, suggesting that the in duction of Hsp72 is blocked downstream to HSF-DNA complex formation by the metabolic alteration occurring during sepsis. The dissociation failure of t he constitutive heat shock element binding factor (CHBF) from the heat shoc k element may play an important role in this negative regulation.