Overexpression of the FGF-2 24-kDa isoform up-regulates IL-6 transcription in NIH-3T3 cells.
We have isolated NIH-3T3 cell lines overexpressing the nuclear 24-kDa isoform of fibroblast growth factor (FGF)-2 and characterized its regulatory effect on the expression of interleukin-6 (IL-6) in these cells. The clone pRF5 expressing the highest level was able to grow in 1% serum medium to a high saturation density and acquired a radioresistance advantage. In pRF5 and another clone pRF1, IL-6 RNA levels were markedly increased. Studies with IL-6 promoter constructs revealed that IL-6 gene up-regulation occurred at the transcriptional level and did not involve the AP-1 binding site. Exogenously added 18-kDa isoform of FGF-2 (100 ng/ml) produced down-regulation of IL-6 involving an AP-1 binding site, thus suggesting a receptor-independent pathway for the intracellular 24-kDa isoform.
INSERM U397, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
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I
Delrieu
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E
Arnaud
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G
Ferjoux
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F
Bayard
J C
JC
Faye
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007536:Isomerism; D051379:Mice; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D015850:Interleukin-6; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2