CSF-1-induced and constitutive Il6 gene expression in mouse macrophages: evidence for PKC-dependent and -independent pathways

Experimental Cell Research
S J KamdarR Evans

Abstract

It has been recently shown that CSF-1 enhanced the constitutive expression of the Il6 gene in resident mouse peritoneal macrophages (PM phi) but little is known about the pathways involved. In this report, we show that both constitutive and CSF-1-induced IL-6 release were enhanced and prolonged in the presence of the PKC inhibitors, staurosporine (SP) and its derivative, GF-109203X. Enhancement of constitutive IL-6 release required higher concentrations of inhibitors, while enhanced CSF-1-induced release was diminished when inhibitor concentrations exceeded defined limits. SP was also shown to activate constitutive IL-6 release by blood monocytes and elicited PM phi but had no effect on their responsiveness to CSF-1. Activation of PKC by exposure of resident PM phi to phorbol myristate acetate (PMA) also resulted in enhanced IL-6 release and PMA was shown to synergize with CSF-1. These data indicate that CSF-1 does not induce Il6 gene expression by amplifying the constitutive pathway in all mononuclear phagocyte subpopulations. It exerts its effects independently of PKC, which may activate Il6 gene expression in its own right by an alternative pathway. While CSF-1 and PKC are involved in separate pathways, the synergistic IL-6 ...Continue Reading

References

Jan 1, 1991·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·M A BrachF Herrmann
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A SenguptaE R Stanley
Aug 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T A Tran-ThiP A Baeuerle
Jan 1, 1994·Journal of Cell Science. Supplement·M F Roussel

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