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Contrasting effects of the protein kinase c inhibitor staurosporine on cytokine and phorbol ester stimulation of fructose 2 6 bisphosphate and prostaglandin e production by fibroblasts in vitro comparative studies using interleukin 1 alpha tumor necrosis factor alpha transforming growth factor beta interferon gamma and 12 o tetradecanoylphorbol 13 acetate



Contrasting effects of the protein kinase c inhibitor staurosporine on cytokine and phorbol ester stimulation of fructose 2 6 bisphosphate and prostaglandin e production by fibroblasts in vitro comparative studies using interleukin 1 alpha tumor necrosis factor alpha transforming growth factor beta interferon gamma and 12 o tetradecanoylphorbol 13 acetate



Biochemical Journal 269(3): 573-578



It is known that both interleukin-1.alpha. (IL-1.alpha.) and 12-O-tetradecanoylphorbol 13-acetate (TPA) promote increases in intracellular levels of the glycolytic regulatory metabolite fructose 2,6-bisphosphate [Fru(2,6)P2] and in the production of prostaglandin E (PGE) by subcultured rheumatoid synovial cells (RSC) and human dermal fibroblasts in vitro. We report here that the protein kinase C inhibitor staurosporine enhanced the IL-1.alpha.-induced increase in [Fru(2,6)P2] and PGE production by RSC, whereas in similar concentrations (3-30 nM) this inhibitor decreased the TPA-induced stimulation of these parameters. Staurosporine produced a similar enhancement of the response to IL-1.alpha. by normal human dermal fibroblasts. The increased PGE production provoked by tumour necrosis factor .alpha. (TNF.alpha.) in RSC was also augmented by staurosporine, but, in contrast, the increases in cellular [Fru(2,6)P2] induced by transforming growth factor .beta. (TGF.beta.) and interferon-.gamma. (IFN-.gamma.) were diminished. Thus the protein kinase C inhibitor staurosporine discriminates not only between the effects produced by IL-1.alpha. and TPA, but also between those of IL-1.alpha. and two other cytokines (but not between IL-1.alpha. and TNF.alpha.). These findings suggest that IL-1.alpha. and probably TNF.alpha. act via an intracellular mechanism different from that mediating the action of TPA, TGF-.beta. and IFN-.gamma., and provide evidence that staurosporine is capable of amplifying the IL-1 signal.

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Accession: 007157080

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PMID: 2117917


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Contrasting effects of the protein kinase C inhibitor, staurosporine, on cytokine and phorbol ester stimulation of fructose 2,6-bisphosphate and prostaglandin E production by fibroblasts in vitro . Comparative studies using interleukin-1 , tumour necrosis factor , transforming growth factor , interferon- and 12- O -tetradecanoylphorbol 13-acetate. Biochemical Journal 269(3): 573-577, 1990

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