Interleukin 1 (IL-1) production is not essential for acquired resistance of human A375 melanoma cells to anti-proliferative effect of IL-1

The proliferation of human melanoma cell line A375-6 is inhibited by interleukin 1 (IL-1). However, the cells acquired resistance to IL-1 after a long period of culture. We have reported that 2 resistant subclones, A375-R8 and -R19, produced IL-1 alpha constitutively and that IL-1 induced IL-6 production in an autocrine manner. Therefore, we supposed that IL-1 alpha production renders the cells resistant to IL-1. To investigate the relationship between IL-1 alpha production and IL-1 resistance, we transfected the IL-1 alpha expression plasmid to the IL-1-sensitive clone, A375-6, and the anti-sense mRNA expression plasmid to IL-1-resistant cells, A375-R8 and -R19. A375-6MS, a transfectant of mature IL-1 alpha expression plasmid, expressed IL-1 alpha mRNA and produced IL-1 activity at a level comparable to the resistant cells. The transfectant also produced IL-6 and exhibited augmented expression of Mn-SOD mRNA. However, IL-1 sensitivity of this transfectant was not affected. With respect to sensitivity to anti-proliferative effects of other cytokines, such as IL-6 and TNF alpha, there was no difference between the transfectant and parent cells. Although A375-R8PHI0 and -R19PH10, transfectants of IL-1 alpha anti-sense mRNA expression plasmid, exhibited a decrease in the level of IL-1 production, their IL-1 sensitivity did not differ from parent cells. These results, therefore, suggest that IL-1 alpha production is not essential or sufficient for the acquisition of resistance to the antiproliferative effect of IL-1. (C) 1996 Wiley-Liss, Inc.