Studies on the regulatory mechanisms of interleukin-8 gene expression in resting and IFN-gamma-treated neutrophils: evidence on the capability of staurosporine of inducing the production of interleukin-8 by human neutrophils.
To understand how expression of IL-8 mRNA is regulated, we studied the effects of Staurosporine, H7, phorbol-myristate-acetate and Dexamethasone in human neutrophils subsequently treated with IFN-gamma. Our results can be summarized as follows: a) IL-8 mRNA steady state levels were enhanced in a dose dependent fashion by both Staurosporine and phorbol-myristate-acetate, were not influenced by H7, but were decreased by Dexamethasone; b) the negative effect of IFN-gamma on IL-8 mRNA accumulation was prevented by Staurosporine and phorbol-myristate-acetate, was not influenced by H7, and was potentiated by Dexamethasone; c) IL-8 mRNA induction caused by Staurosporine was accompanied by a time and dose dependent release of IL-8 into the PMN supernatants.
Cassatella
M A
MA
Institute of General Pathology, Verona, Italy.
Aste
M
M
Calzetti
F
F
Constantin
G
G
Guasparri
I
I
Ceska
M
M
Rossi
F
F
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D015152:Blotting, Northern; D003573:Cytochrome b Group / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics*; D007546:Isoquinolines / Q000494:pharmacology; D019255:NADPH Oxidases; D009504:Neutrophils / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019311:Staurosporine; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D003573:Cytochrome b Group; D016209:Interleukin-8; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D013481:Superoxides; D003907:Dexamethasone; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C036888:cytochrome b558; D019255:NADPH Oxidases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate