title: A small molecule inhibitor for ATPase activity of Hsp70 and Hsc70 enhances the immune response to protein antigens.
abstract: The ATPase activities of Hsp70 and Hsc70 are known to be responsible for regulation of various biological processes. However, little is known about the roles of Hsp70 and Hsc70 in modulation of immune responses to antigens. In the present study, we investigated the effect of apoptozole (Az), a small molecule inhibitor of Hsp70 and Hsc70, on immune responses to protein antigens. The results show that mice administered with both protein antigen and Az produce more antibodies than those treated with antigen alone, showing that Az enhances immune responses to administered antigens. Treatment of mice with Az elicits production of antibodies with a high IgG2c/IgG1 ratio and stimulates the release of Th1 and Th2-type cytokines, suggesting that Az activates the Th1 and Th2 immune responses. The observations made in the present study suggest that inhibition of Hsp70 and Hsc70 activities could be a novel strategy designing small molecule-based adjuvants in protein vaccines.
authors.affiliation: National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Baek
authors.affiliation: Department of Biochemistry, College of Life Science &Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, College of Life Science &Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Bo Ryeong
authors.initials: BR
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science &Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, College of Life Science &Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
authors.forename: Injae
authors.initials: I
authors.lastname: Shin
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001549:Benzamides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006433:Hemocyanins / Q000276:immunology; D007093:Imidazoles / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D001549:Benzamides; D016207:Cytokines; D004791:Enzyme Inhibitors; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D007093:Imidazoles; D007074:Immunoglobulin G; D054852:Small Molecule Libraries; C000608805:apoptozole; D010047:Ovalbumin; D006433:Hemocyanins; D000251:Adenosine Triphosphatases; C032808:keyhole-limpet hemocyanin