title: 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 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.
authors.affiliation: Institute of Cell Biophysics of RAS, Pushchino, Moscow Region 142290, Russia.
authors.forename: Maxim
authors.initials: M
authors.lastname: Vinokurov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ostrov
authors.forename: Marina
authors.initials: M
authors.lastname: Yurinskaya
authors.forename: David
authors.initials: D
authors.lastname: Garbuz
authors.forename: Arkady
authors.initials: A
authors.lastname: Murashev
authors.forename: Olga
authors.initials: O
authors.lastname: Antonova
authors.forename: Mikhail
authors.initials: M
authors.lastname: Evgen'ev
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000097:blood; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008070:Lipopolysaccharides; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012709:Serum Albumin / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism*; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D012709:Serum Albumin; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D001663:Bilirubin