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 l (IL-l). However, the cells acquired resistance to IL-l after a long period of culture. We have reported that 2 resistant subclones, A375-R8 and -R19, produced IL-l alpha constitutively and that IL-l induced IL-6 production in an autocrine manner. Therefore, we supposed that IL-l alpha production renders the cells resistant to IL-l. To investigate the relationship between IL-l alpha production and IL-l resistance, we transfected the IL-l alpha expression plasmid to the IL-l-sensitive clone, A375-6, and the anti-sense mRNA expression plasmid to IL-l-resistant cells, A375-R8 and -R19. A375-6MS, a transfectant of mature IL-l alpha expression plasmid, expressed IL-l alpha mRNA and produced IL-l 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-l 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-R8PH10 and -R19PH10, transfectants of IL-l alpha anti-sense mRNA expression plasmid, exhibited a decrease in the level of IL-l production, their IL-l sensitivity did not differ from parent cells. These results, therefore, suggest that IL-l alpha production is not essential or sufficient for the acquisition of resistance to the anti-proliferative effect of IL-l.
Itoh
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Hayashi
H
H
Watanabe
N
N
Kobayashi
Y
Y
Takii
T
T
Onozaki
K
K
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D016372:RNA, Antisense; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase