Recombinant human Hsp70 protects against lipoteichoic acid-induced inflammation manifestations at the cellular and organismal levels

Abstract

It has been previously reported that pretreatment with exogenous heat shock protein 70 (Hsp70) is able to protect cells and animals from the deleterious effects of bacterial lipopolysaccharide (LPS) produced by Gramnegative bacteria. However, the effects of Hsp70 pretreatment on lipoteichoic acid (LTA) challenge resulted from Gram-positive bacteria infection have not been fully elucidated. In this study, we demonstrated that preconditioning with human recombinant Hsp70 ameliorates various manifestations of systematic inflammation, including reactive oxygen species, TNFα, and CD11b/CD18 adhesion receptor expression induction observed in different myeloid cells after LTA addition. Therefore, exogenous Hsp70 may provide a mechanism for controlling excessive inflammatory responses after macrophage activation. Furthermore, in a rat model of LTA-induced sepsis, we demonstrated that prophylactic administration of exogenous human Hsp70 significantly exacerbated numerous homeostatic and hemodynamic disturbances induced by LTA challenge and partially normalized the coagulation system and multiple biochemical blood parameters, including albumin and bilirubin concentrations, which were severely disturbed after LTA injections. Importantly, prophylactic intravenous injection of Hsp70 before LTA challenge significantly reduced mortality rates. Thus, exogenous mammalian Hsp70 may serve as a powerful cellular defense agent against the deleterious effects of bacterial pathogens, such as LTA and LPS. Taken together, our findings reveal novel functions of this protein and establish exogenous Hsp70 as a promising pharmacological agent for the prophylactic treatment of various types of sepsis.

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice

“…potentially by decreasing reactive oxygen species production and proinflammatory cytokines; an anti-inflammatory effect of eHsp70 has been demonstrated (22,23,(40)(41)(42)(43).…”

The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children

“…Results are expressed as mean; ± SEM. Glutamine ¼ glutamine, LPS ¼ endotoxin *p < 0.05, **p < 0.005. model of sepsis model using, either lipoteichoic acid or LPS, shows that pre-treatment of human neutrophils with recombinant HSP70 prior to the administration of endotoxin attenuates the release of TNF-a [41]. This is corroborated in other in vitro animal models where the use of recombinant HSP70 provides a similar antiinflammatory mode of action by inhibiting C/EBPb and C/EPBd transcription factors from signalling via TLR2-ERK-STAT2-1L10 pathway, attenuating the release of pro-inflammatory mediators [42].…”

Preinduction of heat shock protein 70 protects mice against post-infection irritable bowel syndrome via NF-κB and NOS/NO signaling pathways

“…Compelling evidences have shown that preinduction of HSP70 by heat stress has various beneficial effects in different pathological injury (Dong et al 2013;Fleming et al 2002;Lee et al 2014a;Yang et al 2009). Meanwhile, overexpression or recombinant HSP70 exhibits an anti-inflammatory property in various pathological models (Doeppner et al 2013;Vinokurov et al 2012). However, the effects of HSP70 on PI-IBS have not been reported.…”