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.
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.
复制标题
热休克蛋白（HSP）27和HSP70的体内抑制，通过诱导抗原性无反应性来加速DMBA诱导的皮肤致癌性。
DOI：
10.4049/jimmunol.1402804
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发表时间：
2015-05-15
期刊：
影响因子：
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通讯作者：
Elmets CA
中科院分区：
文献类型：
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作者：
Yusuf N;Nasti TH;Ahmad I;Chowdhury S;Mohiuddin H;Xu H;Athar M;Timares L;Elmets CA
热休克蛋白（HSPs）在小鼠皮肤中组成性表达。HSP27存在于表皮，HSP70在表皮和真皮层均可见。本研究的目的是研究这些蛋白在皮肤化学癌变中的作用，并确定它们对细胞介导的免疫功能的影响是否是一个促成因素。体内抑制HSP27和HSP70可降低C3H/HeN小鼠对7,12-二甲基苯(a)蒽（DMBA）和苯并(a)芘B(a)P的t细胞介导的免疫应答，并导致抗原特异性耐受状态。在小鼠体内进行抗hsp27和抗HSP70抗体预处理后，再进行标准的二阶段DMBA/12- o- tetradecanoylpholl -13-acetate （TPA）皮肤癌变方案，抗hsp27和HSP70预处理小鼠的肿瘤发生率明显高于对照抗体预处理小鼠（p<0.05）。当数据被评估为每组肿瘤的累积数量时，得到了类似的结果。用HSP27和HSP70抗体预处理的小鼠产生更多的H-ras突变和更少的DMBA特异性细胞毒性t淋巴细胞。这些发现表明，在小鼠中，HSP27和HSP70在诱导细胞介导的对致癌多芳烃的免疫中起关键作用。增强对致癌多芳烃的免疫反应可能是预防它们产生的肿瘤的有效方法。
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 if 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 B(a)P in C3H/HeN mice and resulted in a state of antigen specific tolerance. When mice were pre-treated with anti-HSP27 and anti-HSP70 antibodies in vivo prior to subjecting them to a standard two-stage DMBA/12-O-tetradecanoylphorbol-13-acetate (TPA) cutaneous carcinogenesis protocol, the percentage of mice with tumors was much greater (p<0.05) in anti-HSP27 and HSP70 pre-treated animals compared to mice pre-treated with control antibody. Similar results were obtained when the data were evaluated as the cumulative number of tumors per group. Mice pre-treated with HSP27 and HSP70 antibodies 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.