Lin T H, Chu T M
Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Cancer Institute, New York State Department of Health, Buffalo 14263.
Biochem Biophys Res Commun. 1993 Mar 31;191(3):937-42. doi: 10.1006/bbrc.1993.1307.
We previously demonstrated that interleukin-2 induced murine lymphokine-activated killer cell activity is augmented by retinoic acid. The enhanced cytotoxicity is significantly correlated with the increase in PKC. In the present study, we have shown that retinoic acid increases the expression of perforin, a potent cytolytic mediator, at both protein and mRNA levels. This enhancement can be induced by a direct stimulation of PKC signaling pathway, as manipulated by a short term incubation of lymphokine-activated killer cells with 12-O-tetradecanoyl-phorbol-13-acetate and ionomycin, and suppressed by PKC inhibitors. These results suggest that PKC plays a regulatory role in the enhancement of the expression of cytolytic mediators in retinoic acid-augmented lymphokine-activated killer cells.
我们先前证明，视黄酸可增强白细胞介素-2诱导的小鼠淋巴因子激活的杀伤细胞活性。细胞毒性增强与蛋白激酶C（PKC）的增加显著相关。在本研究中，我们发现视黄酸在蛋白质和mRNA水平上均增加了穿孔素（一种有效的溶细胞介质）的表达。这种增强可通过直接刺激PKC信号通路来诱导，方法是将淋巴因子激活的杀伤细胞与12-O-十四烷酰佛波醇-13-乙酸酯和离子霉素短期孵育来实现，并且可被PKC抑制剂抑制。这些结果表明，PKC在视黄酸增强的淋巴因子激活的杀伤细胞中溶细胞介质表达的增强中起调节作用。
