Celada A, Maki R A
La Jolla Cancer Research Foundation, CA 92037.
J Immunol. 1991 Jan 1;146(1):114-20.
The mechanism of gene expression for the MHC I-A beta and TNF genes was studied in murine bone marrow macrophages. The treatment of macrophages with PMA stimulated the expression of TNF, but not I-A beta, suggesting that the TNF gene is responsive to activators of protein kinase C whereas the I-A beta gene is not. The treatment of macrophages with IFN-gamma led to an increase in the level of RNA for both TNF and I-A beta. The increase in expression of I-A beta and TNF, induced by IFN-gamma, was blocked by naphthalenesulfonamide or phenothiazine (trifluoperazine) but was not affected by the addition of isoquinolinesulfonamide or sphingosine. These results suggest that the induced expression of I-A beta and TNF by IFN-gamma is mediated by a pathway that is protein kinase C independent. This was supported by the finding that calcium ionophores were also able to induce the gene expression of both TNF and I-A beta. We observed that when both IFN-gamma and PMA were added to the macrophages, the level of RNA for TNF increased to a higher level than the level seen when either agent alone was added to the cells. In contrast, the addition of both IFN-gamma and PMA to macrophages had an inhibitory effect on the expression of the I-A beta gene. These results further emphasize the complex nature of gene regulation during the activation of macrophages.
在小鼠骨髓巨噬细胞中研究了MHC I-Aβ和TNF基因的基因表达机制。用佛波酯（PMA）处理巨噬细胞可刺激TNF的表达，但不刺激I-Aβ的表达，这表明TNF基因对蛋白激酶C的激活剂有反应，而I-Aβ基因则没有。用γ干扰素（IFN-γ）处理巨噬细胞会导致TNF和I-Aβ的RNA水平升高。IFN-γ诱导的I-Aβ和TNF表达增加被萘磺酰胺或吩噻嗪（三氟拉嗪）阻断，但不受异喹啉磺酰胺或鞘氨醇添加的影响。这些结果表明，IFN-γ诱导的I-Aβ和TNF表达是由一条不依赖蛋白激酶C的途径介导的。钙离子载体也能够诱导TNF和I-Aβ的基因表达，这一发现支持了上述结论。我们观察到，当将IFN-γ和PMA都添加到巨噬细胞中时，TNF的RNA水平比单独添加任何一种试剂时观察到的水平升高到更高水平。相反，将IFN-γ和PMA都添加到巨噬细胞中对I-Aβ基因的表达有抑制作用。这些结果进一步强调了巨噬细胞激活过程中基因调控的复杂性。
