In Vivo Suppression of Heat Shock Protein (HSP)27 and HSP70 Accelerates DMBA-Induced Skin Carcinogenesis by Inducing Antigenic Unresponsiveness to the Initiating Carcinogenic Chemical.

Abstract

Heat shock proteins (HSPs) are constitutively expressed in murine skin. HSP27 is present in the epidermis, and HSP70 can be found in both the epidermis and dermis. The purpose of this study was to investigate the role of these proteins in cutaneous chemical carcinogenesis and to determine whether their effects on cell-mediated immune function were a contributing factor. In vivo inhibition of HSP27 and HSP70 produced a reduction in the T cell-mediated immune response to 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene in C3H/HeN mice and resulted in a state of Ag-specific tolerance. When mice were pretreated with anti-HSP27 and anti-HSP70 Abs in vivo prior to subjecting them to a standard two-stage DMBA/12-O-tetradecanoylphorbol-13-acetate cutaneous carcinogenesis protocol, the percentage of mice with tumors was much greater (p < 0.05) in anti-HSP27- and HSP70-pretreated animals compared with mice pretreated with control Ab. Similar results were obtained when the data were evaluated as the cumulative number of tumors per group. Mice pretreated with HSP27 and HSP70 Abs developed more H-ras mutations and fewer DMBA-specific cytotoxic T lymphocytes. These findings indicate that in mice HSP27 and HSP70 play a key role in the induction of cell-mediated immunity to carcinogenic polyaromatic hydrocarbons. Bolstering the immune response to carcinogenic polyaromatic hydrocarbons may be an effective method for prevention of the tumors that they produce.

• Authors: Nabiha Yusuf, Tahseen H Nasti, Israr Ahmad, Sanim Chowdhury, Hasan Mohiuddin, Hui Xu, Mohammad Athar, Laura Timares, Craig A Elmets
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 194 Issue 10 Pg. 4796-803 (May 15 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 25840912 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• Carcinogens
• HSP27 Heat-Shock Proteins
• HSP70 Heat-Shock Proteins
• 9,10-Dimethyl-1,2-benzanthracene

Topics

• 9,10-Dimethyl-1,2-benzanthracene (immunology, toxicity)
• Animals
• Carcinogenesis (immunology)
• Carcinogens (toxicity)
• Disease Models, Animal
• Female
• HSP27 Heat-Shock Proteins (immunology)
• HSP70 Heat-Shock Proteins (immunology)
• Immune Tolerance (immunology)
• Mice
• Mice, Inbred C3H
• Skin Neoplasms (chemically induced, immunology, metabolism)