Yusuf Nabiha, Nasti Tahseen H, Ahmad Israr, Chowdhury Sanim, Mohiuddin Hasan, Xu Hui, Athar Mohammad, Timares Laura, Elmets Craig A
Department of Dermatology and Skin Diseases Research Center, University of Alabama, Birmingham, AL 35294; and Veteran Affairs Medical Center, Birmingham, AL 35294
Department of Dermatology and Skin Diseases Research Center, University of Alabama, Birmingham, AL 35294; and.
J Immunol. 2015 May 15;194(10):4796-803. doi: 10.4049/jimmunol.1402804. Epub 2015 Apr 3.
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.
热休克蛋白（HSPs）在小鼠皮肤中组成性表达。HSP27存在于表皮中，而HSP70在表皮和真皮中均有发现。本研究的目的是探讨这些蛋白在皮肤化学致癌作用中的作用，并确定它们对细胞介导免疫功能的影响是否是一个促成因素。在体内抑制HSP27和HSP70会导致C3H/HeN小鼠对7,12-二甲基苯并(a)蒽（DMBA）和苯并(a)芘的T细胞介导免疫反应降低，并导致抗原特异性耐受状态。当小鼠在接受标准的两阶段DMBA/12-O-十四酰佛波醇-13-乙酸皮肤致癌方案之前，在体内用抗HSP27和抗HSP70抗体进行预处理时，与用对照抗体预处理的小鼠相比，抗HSP27和HSP70预处理的动物中出现肿瘤的小鼠百分比要高得多（p<0.05）。当将数据评估为每组肿瘤的累积数量时，也获得了类似的结果。用HSP27和HSP70抗体预处理的小鼠发生更多的H-ras突变，而DMBA特异性细胞毒性T淋巴细胞减少。这些发现表明，在小鼠中，HSP27和HSP70在诱导对致癌多环芳烃的细胞介导免疫中起关键作用。增强对致癌多环芳烃的免疫反应可能是预防它们所产生肿瘤的有效方法。
