STIMULATORY EFFECT OF INTERLEUKIN-1-ALPHA ON PROLIFERATION THROUGH A CA2+ CALMODULIN-DEPENDENT 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 interleuk in-la (IL-la) and granulocyte-colony stimulating factor. In the presen t study, we investigated the signal transduction pathway in the prolif eration of NIM 1 cells evoked by IL-1 alpha. Incubation of NIM 1 cells with IL-1 alpha for 48 h increased the incorporation of H-3-thymidine (H-3-TdR). The stimulatory effect of IL-l alpha was evident at 0.01 n g/ml and the maximal effect was seen at 10 ng/ml. IL-1 alpha evoked an influx of Ca-45 into NIM 1 cells within 3 min in a concentration-depe ndent manner (0.01-1 ng/ml). These stimulatory effects of IL-lcr on bo th H-3-TdR incorporation and Ca-45 influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca2+ channels, in a con centration-dependent manner (10-1000 nM). The stimulatory effect of IL -1 alpha on H-3-TdR incorporation was inhibited by N-(6-aminohexyl)-5- chloro-1-naphthalenes amide (W-7), an antagonist of calmodulin, but no t by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibito r of protein kinase C. While the culture medium initially contained 0. 75 mM Ca2+, inhibition of H-3-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results su ggest that IL-1 alpha stimulates cell proliferation through a Ca2+/cal modulin-dependent pathway in NIM 1 cells.