Stimulatory Effect of Interleukin‐1α on Proliferation through a Ca2+/Calmodulindependent Pathway of a Human Thyroid Carcinoma Cell Line, NIM 1

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1α (IL-1α) and granulocyte-colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL-1α. Incubation of NIM 1 cells with IL-1α for 48 h increased the incorporation of 3 H-thymidine ( 3 H-TdR). The stimulatory effect of IL-1α was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-la evoked an influx of 45 Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01-1 ng/ml). These stimulatory effects of IL-1α on both 3 H-TdR incorporation and 45 Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca 2+ channels, in a concentration-dependent manner (10-1000 nM). The stimulatory effect of IL-1α on 3 H-TdR incorporation was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), an antagonist of calmodulin, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 mM Ca 2+ , inhibition of 3 H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1α stimulates cell proliferation through a Ca 2+ /calmodulin-dependent pathway in NIM 1 cells.