INTERLEUKIN-1 (IL-1) PRODUCTION IS NOT ESSENTIAL FOR ACQUIRED-RESISTANCE OF HUMAN A375 MELANOMA-CELLS TO ANTIPROLIFERATIVE EFFECT OF IL-1

The proliferation of human melanoma cell line A375-6 is inhibited by i nterleukin 1 (IL-1). However, the cells acquired resistance to IL-1 af ter a long period of culture. We have reported that 2 resistant subclo nes, A375-R8 and -R19, produced IL-1 alpha constitutively and that IL- 1 induced IL-6 production in an autocrine manner. Therefore, we suppos ed that IL-1 alpha production renders the cells resistant to IL-1. To investigate the relationship between IL-1 alpha production and IL-1 re sistance, we transfected the IL-1 alpha expression plasmid to the IL-1 -sensitive clone, A375-6, and the anti-sense mRNA expression plasmid t o 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 pr oduced 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 a ffected. With respect to sensitivity to anti-proliferative effects of other cytokines, such as IL-6 and TNF alpha, there was no difference b etween the transfectant and parent cells. Although A375-R8PHI0 and -R1 9PH10, transfectants of IL-1 alpha anti-sense mRNA expression plasmid, exhibited a decrease in the level of IL-1 production, their IL-1 sens itivity did not differ from parent cells. These results, therefore, su ggest that IL-1 alpha production is not essential or sufficient for th e acquisition of resistance to the antiproliferative effect of IL-1. ( C) 1996 Wiley-Liss, Inc.