Calmodulin regulates the interleukin 1-induced procollagenase production in human uterine cervical fibroblasts.
Interleukin 1 (IL-1) stimulates the synthesis of collagenase in human uterine cervical fibroblasts. This inductive effect of IL-1 on collagenase production was augmented by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a specific inhibitor of calmodulin, in a dose-dependent manner. The apparent collagenase activity observed in the culture medium of the cells treated with IL-1 and 40 microM W-7 was about three times higher than that produced by the cells treated with IL-1 alone. The immunoblotting with the specific antibody against human collagenase showed that the increased collagenase activity resulted from the accelerated biosynthesis of collagenase. Another calmodulin inhibitor, trifluoperazine, enhanced the effect of IL-1 on collagenase production similarly. However, the effect of N-(6-aminohexyl)-1-naphthalenesulfonamide, the weakest inhibitor of calmodulin, was negligible. These results suggest that W-7 enhances the collagenase production by specifically inhibiting calmodulin and that calmodulin may act as a suppressor of the IL-1-induced collagenase production in human uterine cervical fibroblasts.
Ojima
Y
Y
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
Ito
A
A
Nagase
H
H
Mori
Y
Y
D000328:Adult; D015153:Blotting, Western; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism*; D017364:Collagenases; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000502:physiology; D003012:Microbial Collagenase / Q000096:biosynthesis*; D008970:Molecular Weight; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D004792:Enzyme Precursors; D007375:Interleukin-1; D013449:Sulfonamides; D014268:Trifluoperazine; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase