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

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Cell Stress and Chaperones Aims and scope

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 Gram-negative 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.

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Acknowledgements

Work was supported by the Russian Foundation for Basic Research, project 09-04-00643 and 09-04-00660, project from “Genofond dynamics” program, Grant of the Program of Molecular and Cellular Biology RAN to M.E.

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology of RAS, Vavilova, 32, Moscow, 119991, Russia

    David Garbuz & Mikhail Evgen’ev

  2. Institute of Cell Biophysics of RAS, Pushchino, Moscow Region, 142290, Russia

    Maxim Vinokurov, Marina Yurinskaya, Olga Antonova & Mikhail Evgen’ev

  3. Branch of Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of RAS, Pushchino, Moscow Region, 142290, Russia

    Vladimir Ostrov & Arkady Murashev

  4. Pushchino State University, Pushchino, Moscow Region, 142290, Russia

    Maxim Vinokurov & Olga Antonova

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  1. Maxim Vinokurov
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  2. Vladimir Ostrov
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  3. Marina Yurinskaya
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  4. David Garbuz
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  5. Arkady Murashev
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  7. Mikhail Evgen’ev
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Correspondence to Mikhail Evgen’ev.

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Vinokurov, M., Ostrov, V., Yurinskaya, M. et al. Recombinant human Hsp70 protects against lipoteichoic acid-induced inflammation manifestations at the cellular and organismal levels. Cell Stress and Chaperones 17, 89–101 (2012). https://doi.org/10.1007/s12192-011-0288-0

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