Stimulatory Effect of Interleukin‐1α on Proliferation through a Ca(2+)/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‐1α 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.