Koide Y, Ina Y, Nezu N, Yoshida T O
Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Japan.
Proc Natl Acad Sci U S A. 1988 May;85(9):3120-4. doi: 10.1073/pnas.85.9.3120.
Interferon gamma (IFN-gamma) induces HLA-DR and -DQ molecules and causes an accumulation of transcripts in HL-60 cells. Experiments were, therefore, designed to investigate the intracellular signaling molecules regulating the appearance of HLA class II molecules. The expression of HLA class II (DR and DQ) molecules induced by IFN-gamma was blocked by a calmodulin antagonist, W7, but not by a protein kinase C inhibitor, H7. Furthermore, a direct activator of protein kinase C, phorbol 12-myristate 13-acetate, was unable to induce HLA class II (DR) molecule expression. These results suggest that IFN-gamma induces HLA class II molecules on HL-60 cells by way of a calcium-calmodulin pathway and not by way of a protein kinase C pathway. Calmodulin is activated by a transient rise in the cytosolic free calcium. In fact, IFN-gamma evoked a calcium influx into HL-60 cells, whereas depletion of Ca2+ from culture medium resulted in a failure of IFN-gamma to induce DR expression. Furthermore, the calcium ionophore A23187 by itself induced DR molecule expression. These results suggest that IFN-gamma stimulates calcium influx by a so-called receptor-mediated calcium channel and activates the calmodulin branch of the calcium messenger system, resulting in the induction of DR molecules on the surface of HL-60 cells.
γ干扰素（IFN-γ）可诱导HL-60细胞表达HLA-DR和-DQ分子，并使转录本积累。因此，设计实验以研究调节HLA-II类分子出现的细胞内信号分子。IFN-γ诱导的HLA-II类（DR和DQ）分子表达被钙调蛋白拮抗剂W7阻断，但未被蛋白激酶C抑制剂H7阻断。此外，蛋白激酶C的直接激活剂佛波酯12-肉豆蔻酸酯13-乙酸酯无法诱导HLA-II类（DR）分子表达。这些结果表明，IFN-γ通过钙-钙调蛋白途径而非蛋白激酶C途径诱导HL-60细胞表达HLA-II类分子。钙调蛋白由胞质游离钙的短暂升高激活。事实上，IFN-γ引起HL-60细胞钙内流，而培养基中Ca2+的耗尽导致IFN-γ无法诱导DR表达。此外，钙离子载体A23187本身可诱导DR分子表达。这些结果表明，IFN-γ通过所谓的受体介导的钙通道刺激钙内流，并激活钙信使系统的钙调蛋白分支，从而导致HL-6
