title: Stimulatory effect of interleukin-1 alpha on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM 1.
abstract: NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1 alpha (IL-1 alpha) 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-1 alpha. Incubation of NIM 1 cells with IL-1 alpha for 48 h increased the incorporation of 3H-thymidine (3H-TdR). The stimulatory effect of IL-1 alpha was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-1 alpha evoked an influx of 45Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01-1 ng/ml). These stimulatory effects of IL-1 alpha on both 3H-TdR incorporation and 45Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca2+ channels, in a concentration-dependent manner (10-1000 nM). The stimulatory effect of IL-1 alpha on 3H-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 Ca2+, inhibition of 3H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1 alpha stimulates cell proliferation through a Ca2+/calmodulin-dependent pathway in NIM 1 cells.
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu.
authors.forename: N
authors.initials: N
authors.lastname: Inokuchi
authors.forename: K
authors.initials: K
authors.lastname: Zeki
authors.forename: I
authors.initials: I
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Fujihira
authors.forename: U
authors.initials: U
authors.lastname: Yamashita
authors.forename: N
authors.initials: N
authors.lastname: Yanagihara
authors.forename: F
authors.initials: F
authors.lastname: Izumi
authors.forename: S
authors.initials: S
authors.lastname: Eto
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D009529:Nicardipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013964:Thyroid Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D002147:Calmodulin; D004273:DNA, Neoplasm; D007375:Interleukin-1; D013449:Sulfonamides; D005576:Colforsin; C017967:W 7; D009529:Nicardipine; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium; D013936:Thymidine