PMID- 1883525 OWN - NLM STAT- MEDLINE DCOM- 19911008 LR - 20220227 IS - 1015-2008 (Print) IS - 1015-2008 (Linking) VI - 59 IP - 4 DP - 1991 TI - Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B. PG - 284-8 AB - 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. FAU - Brach, M A AU - Brach MA AD - Department of Internal Medicine 1, University of Freiburg Medical Center, FRG. FAU - Henschler, R AU - Henschler R FAU - Mertelsmann, R H AU - Mertelsmann RH FAU - Herrmann, F AU - Herrmann F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Pathobiology JT - Pathobiology : journal of immunopathology, molecular and cellular biology JID - 9007504 RN - 0 (DNA Probes) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 9007-49-2 (DNA) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Base Sequence MH - DNA/genetics MH - DNA Probes MH - Gene Expression Regulation MH - Humans MH - In Vitro Techniques MH - Macrophage Colony-Stimulating Factor/*biosynthesis/genetics/pharmacology MH - Molecular Sequence Data MH - Monocytes/drug effects/metabolism MH - NF-kappa B/*metabolism MH - Protein Kinase C/*metabolism MH - RNA, Messenger/genetics/metabolism MH - Transcription, Genetic EDAT- 1991/01/01 00:00 MHDA- 1991/01/01 00:01 CRDT- 1991/01/01 00:00 PHST- 1991/01/01 00:00 [pubmed] PHST- 1991/01/01 00:01 [medline] PHST- 1991/01/01 00:00 [entrez] AID - 10.1159/000163664 [doi] PST - ppublish SO - Pathobiology. 1991;59(4):284-8. doi: 10.1159/000163664.