Effect of calmodulin antagonists on the interferon system: induction and action of interferons.
Synthesis of interferon (IFN) in response to Sendai virus and the development of the resulting antiviral state were studied in human (BG-9) and murine (L-929) fibroblast cell cultures in the presence of the calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). Compared to control cultures, 16-fold and 8-fold more IFN was formed in human and murine cells, respectively, when 10 microM TFP was present in the medium for 24 h prior to IFN induction with Sendai virus. W-7 did not affect IFN production in human cells, but enhanced it in L-929 cells by 4- to 8-fold. TFP inhibited the antiviral state induced by homologous IFN in the two cell systems, and at 20 microM, there was a 3,000-fold increase in vesicular stomatitis virus (VSV) yield. It also reduced the maintenance of the antiviral state in human cells. In contrast, W-7 had no effect on the development of the antiviral state in either of the two cell systems. Thus, calcium-calmodulin dependent cellular processes are involved in both induction of IFN and its action. The several patterns response to TFP and W-7 may reflect different ligand-binding sites on calmodulin.
Department of Microbiology, State University of New York, Buffalo 14214.
H Y
HY
Lin
P J
PJ
Davis
F B
FB
Davis
K C
KC
Chadha
H R
HR
Thacore
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D006801:Humans; D007369:Interferon Inducers; D007372:Interferons / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*
D002147:Calmodulin; D007369:Interferon Inducers; D013449:Sulfonamides; D014268:Trifluoperazine; C017967:W 7; D007372:Interferons