title: The potential role of the macrophage colony-stimulating factor, CSF-1, in inflammatory responses: characterization of macrophage cytokine gene expression.
abstract: In this report we report that recombinant human monocyte-macrophage colony-stimulating factor-1 (CSF-1) induces resident murine peritoneal cells (PCs) to transcribe several inflammatory cytokine genes, including interleukin (IL)-1 alpha, IL-1 beta, IL-6, and granulocyte-macrophage CSF in a dose-dependent and time-related manner. Peak mRNA levels were seen between 4 and 6 h. CSF-1 did not modulate the expression of tumor necrosis factor-alpha mRNA. The serum content of the culture medium appeared to regulate both the extent of CSF-1-induced gene transcription and the adherence properties of the cells. Decreasing the serum concentration significantly reduced CSF-1-induced transcription and was associated with the rapid spreading of the majority of the adherent cells. This reduced sensitivity to CSF-1 was paralleled by a markedly lower levels of c-fms mRNA encoding the CSF-1 receptor. Induced gene transcription was followed by the release of large quantities of IL-6 only. IL-1 activity remained associated with the cells. Neither supernatant nor cell lysate granulocyte-macrophage CSF activity was inducible above the low levels associated with control cultures. Evidence that the mononuclear phagocytes, as opposed to B or T cells, were the targets of CSF-1 was obtained in two ways: (1) PCs from B6 scid/scid and NOD scid/scid mice consisting of 78-86% MAC-1+, F4/80+ cells and few B or T cells, as shown by flow cytometry analysis, released 5- to 10-fold more IL-6 in response to CSF-1 stimulation than B6 PCs, which contained approximately 30% double-positive cells, and (2) pretreatment of B6 PCs with antibodies to the CSF-1 receptor blocked the CSF-1-induced secretion of IL-6. These data suggest that CSF-1 primes noninflammatory mononuclear phagocytes for a role in inflammatory responses but does not provide the necessary signals for either secretion or translation of all cytokines equally.
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: R
authors.initials: R
authors.lastname: Evans
authors.forename: S J
authors.initials: SJ
authors.lastname: Kamdar
authors.forename: J A
authors.initials: JA
authors.lastname: Fuller
authors.forename: D M
authors.initials: DM
authors.lastname: Krupke
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor