Reduction of perforin, granzyme b, and cytokine interferon γ by ethanol in male Fischer 344 rats
Reduction of perforin, granzyme b, and cytokine interferon γ by ethanol in male Fischer 344 rats
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DOI：
10.1097/01.alc.0000060528.53113.5c
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发表时间：
2003-04-01
影响因子：
3.2
通讯作者：
Sarkar, DK
中科院分区：
文献类型：
--
作者：
Dokur, M;Boyadjieva, NI;Sarkar, DK
背景：长期饮酒会损害免疫系统，增加患癌症和感染的风险。自然杀伤（NK）细胞是抵御病毒、细菌和真菌感染的第一道防线，在细胞抵抗恶性肿瘤和肿瘤转移中起着重要作用。我们以前已经表明，乙醇管理抑制NK细胞的细胞溶解活性在雄性费舍尔大鼠。本研究分析了乙醇对调节NK细胞溶解活性的穿孔素、颗粒酶B和细胞因子干扰素(IFN)- γ的影响，了解乙醇抑制NK细胞活性的分子机制。方法：雄性Fischer大鼠饲喂含乙醇（8.7% v/v）饲料，对照组饲喂等热量饲料。在2周结束时，将动物斩首，立即切除脾脏组织，用于分析NK细胞的细胞溶解活性、穿孔素、颗粒酶B和ifn - γ信使RNA （mRNA）或蛋白质水平。采用实时定量聚合酶链反应评估穿孔素、颗粒酶B和ifn - γ mRNA水平，并采用Western blot、酶联免疫吸附试验或酶活性试验分析这些因子的蛋白水平。结果：与配对饲养的动物相比，乙醇降低了NK细胞的细胞溶解活性，降低了穿孔素、颗粒酶B和ifn - γ mRNA的表达。与配对饲养的动物相比，乙醇还显著降低了酒精喂养动物的穿孔素和ifn - γ蛋白水平以及颗粒酶h酶活性。结论：这些数据表明，慢性乙醇消耗可能通过降低颗粒酶B、穿孔素和ifn - γ的产生和活性来抑制雄性Fischer大鼠NK细胞的细胞溶解活性。
Background: Chronic alcohol consumption can impair the immune system and predispose individuals to an increased risk of cancer and infection. Natural killer (NK) cells are the first line of defense against viral, bacterial, and fungal infections and play an important role in cellular resistance to malignancy and tumor metastasis. We have shown previously that ethanol administration suppresses NK cell cytolytic activity in male Fischer rats. This study analyzed the effects of ethanol on perforin, granzyme B, and the cytokine interferon (IFN)-gamma, factors that modulate NK cell cytolytic activity, to understand the molecular mechanism involved in ethanol's suppression of NK cell activity.Methods: A group of male Fischer rats was fed an ethanol-containing diet (8.7% v/v), whereas a control group was pair-fed an isocaloric diet. At the end of 2 weeks, animals were decapitated, and spleen tissues were immediately removed and used for analysis of NK cell cytolytic activity, perforin, granzyme B, and IFN-gamma messenger RNA (mRNA) or protein levels. The mRNA levels of perforin, granzyme B, and IFN-gamma were evaluated by quantitative real-time polymerase chain reaction, and protein levels of these factors were analyzed by Western blot, enzyme-linked immunosorbent assay, or enzymatic activity assay.Results: Ethanol reduced the NK cell cytolytic activity and decreased the mRNA expression of perforin, granzyme B, and IFN-gamma in ethanol-fed animals when compared with pair-fed animals. Ethanol also significantly reduced the protein levels of perforin and IFN-gamma and the enzyme activity of granzyme h in alcohol-fed animals as Compared with pair-fed animals.Conclusions: These data suggest that chronic ethanol consumption may suppress NK cell cytolytic activity in male Fischer rats by decreasing the production, activity, or both of granzyme B, perforin, and IFN-gamma.