title: Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B.
abstract: Macrophage-colony-stimulating factor (M-CSF), also referred to as CSF-1, regulates the survival, growth, differentiation and functional activity of monocytes by binding to a single class of high-affinity cell surface receptors, known to be the product of the c-fms protooncogene. The detection of both M-CSF and c-fms expression by cells of the monocyte lineage has suggested that M-CSF may act by an autocrine mechanism. Interestingly, it has been shown that M-CSF can induce the expression of its own gene. Although sensitivity to M-CSF can be modulated by regulation of receptor expression and function, M-CSF responsiveness is largely determined at a postreceptor level. To date, little is known about the intracellular pathway of M-CSF signal transduction. We have therefore investigated the changes in protein kinase C (PKC) activity upon exposure of monocytes to M-CSF. We show that M-CSF activates and translocates PKC. Inhibition of PKC by the isoquinoline derivative H7 abolishes induction of M-CSF by M-CSF. Furthermore, activation of PKC was pertussis-toxin-sensitive and was associated with the detection of an NF kappa B protein in nuclear extracts of M-CSF-induced blood monocytes but not in monocytes exposed to medium treatment only. The results suggest that M-CSF induction of M-CSF involves G proteins, PKC and NF kappa B.
authors.affiliation: Department of Internal Medicine 1, University of Freiburg Medical Center, FRG.
authors.forename: M A
authors.initials: MA
authors.lastname: Brach
authors.forename: R
authors.initials: R
authors.lastname: Henschler
authors.forename: R H
authors.initials: RH
authors.lastname: Mertelsmann
authors.forename: F
authors.initials: F
authors.lastname: Herrmann
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D015342:DNA Probes; D016328:NF-kappa B; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D011493:Protein Kinase C