Ca2+-ATPase inhibitor induces IL-4 and MCP-1 production in RBL-2H3 cells.
The effects of a Ca2(+)-ATPase inhibitor, cyclopiazonic acid (CPA), and two hydroquinone-antioxidants, 2,5-di-(tert-butyl)-1,4-hydroquinone (DTBHQ) and 2,5-di-(tert-amyl)-1,4-hydroquinone (DTAHQ) on the release of IL-4 and MCP-1 from RBL-2H3 cells were investigated. CPA, DTBHQ and DTAHQ, all of which induce intracellular free Ca2+ concentration ([Ca2+]i) increase, induced IL-4 and MCP-1 release in a dose-dependent manner. The release of TNF-alpha required both a Ca2(+)-ATPase inhibitor and 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the Ca2(+)-ATPase inhibitors induced IL-4 and MCP-1 production without TPA. The release of IL-4 and MCP-1 reached a maximum at 9 and 6 h, respectively. IL-4 and MCP-I release was inhibited by treatment with the immunosuppressant FK-506 and actinomycin D. Therefore, in our system IL-4 and MCP-1 release involves Ca2(+)-dependent and FK-506-sensitive signaling pathways. This is the first report about Th-2 type cytokine and chemokine production in RBL-2H3 cells.
Onose
J
J
Meiji College of Pharmacy, Tokyo, Japan.
Teshima
R
R
Sawada
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D018932:Chemokine CCL2 / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006873:Hydroquinones / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C026297:2,5-ditertiary amyl hydroquinone; D000975:Antioxidants; D018932:Chemokine CCL2; D006873:Hydroquinones; D007211:Indoles; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D015847:Interleukin-4; C019359:2,5-di-tert-butylhydroquinone; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D016559:Tacrolimus; C000543:cyclopiazonic acid