Interleukin-4 regulates mRNA accumulation of macrophage-colony stimulating factor by fibroblasts: synergism with interleukin-1 beta.
We demonstrate that macrophage-colony stimulating factor (M-CSF) is expressed in human fibroblasts at the mRNA and protein level. Following activation with both interleukin (IL)-1 beta and IL-4, fibroblasts synthesized M-CSF transcripts detectable by Northern blot analysis with peak expression occurring at 8 h and 12 h, respectively. Exposure of fibroblasts to both cytokines resulted in M-CSF protein release at 60 h of c. 500 U/ml (for IL-1 beta) and 1000 U/ml (for IL-4), relative to a control preparation of recombinant human M-CSF in a murine bone marrow colony assay. Both interleukins synergized to enhance M-CSF mRNA accumulation and their ability to induce M-CSF transcripts could be abolished by treatment with specific neutralizing antibodies. These observations provide support for the idea that fibroblasts may control monocyte/macrophage development and function, and that IL-1 beta and IL-4 are involved in the regulation of this process.
Henschler
R
R
Department of Internal Medicine I, Albert-Ludwigs-Universität, Freiburg, F.R.G.
Mantovani
L
L
Oster
W
W
Lübbert
M
M
Lindemann
A
A
Mertelsmann
R
R
Herrmann
F
F
D015152:Blotting, Northern; D002478:Cells, Cultured; D004357:Drug Synergism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000502:physiology
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor