Overexpression of the FGF-2 24-kDa isoform up-regulates IL-6 transcription in NIH-3T3 cells

• Published in: FEBS letters 1998-09, Vol.436 (1), p.17-22
• Main Authors: Delrieu, Isabelle, Arnaud, Emmanuelle, Ferjoux, Géraldine, Bayard, Francis, Faye, Jean Charles
• Format: Article
• Language: English
• Subjects: 3T3 Cells - drug effects; 3T3 Cells - metabolism; Animals; Cell Line; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Fibroblast Growth Factor 2 - pharmacology; Fibroblast growth factor-2; Gene Expression Regulation; Gene regulation; Interleukin-6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-6 promoter; Isomerism; Mice; NIH-3T3 cell; Promoter Regions, Genetic; Recombinant Proteins; Transcription Factor AP-1 - metabolism; Transcription, Genetic; Transfection; Up-Regulation
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01086-2

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.