Regulation of NFIL-6 and IL-6 expression by basic fibroblast growth factor in osteoblasts

Abstract

We determined whether basic fibroblast growth factor (bFGF) regulated the expression of IL-6 and NFIL-6 in osteoblasts. In mouse osteoblastic MC3T3-E1 cells, bFGF (10(-8) M) increased NFIL-6 mRNA 2-fold at 30 minutes and 3-fold at 2 h. IL-6 mRNA was increased by bFGF 10(-8) M after 1 h. IL-6 protein was detectable in control cultures but was significantly increased by bFGF (10(-8) M) at 4 h. Immunofluorescence analysis of MC3T3-E1 cells showed primarily cytoplasmic and perinuclear NFIL-6 staining in control cultures while bFGF-treated cells showed increased NFIL-6 staining at 2 and 4 h. Western blotting revealed that bFGF increased NFIL-6 protein at 2 h. In calvarial mouse osteoblasts, bFGF 10(-8) M induced IL-6 mRNA as early as 1 h and significantly increased IL-6 protein levels as early as 2 h. In conclusion, bFGF stimulates IL-6 and NFIL-6 mRNA in osteoblasts. The increase in NFIL-6 mRNA was associated with increased NFIL-6 protein. The increase in IL-6 mRNA was also associated with increased IL-6 protein. We propose that activations of NFIL-6 and IL-6 may be important mediators of the effects of bFGF on bone cells.

Basic Fibroblast Growth Factor Regulates REX1 Expression Via IL‐6 In Stem Cells Isolated From Human Exfoliated Deciduous Teeth

“…In MC3T3‐E1 cells, bFGF promoted nuclear factor interleukin‐6 (NFIL‐6) production and cycloheximide failed to inhibit the bFGF‐induced NFIL‐6 and IL‐6 expression [Hurley et al, ]. Corresponding with this study, we found that the effect of bFGF on IL‐6 expression in SHEDs was not inhibited by cycloheximide treatment.…”

Fibroblast Growth Factor 2 as an Antifibrotic: Antagonism of Myofibroblast Differentiation and Suppression of Pro-Fibrotic Gene Expression

“…This shift included dysregulation of a substantial number of genes involved in inflammation, cytokine signaling, extracellular matrix deposition, and cytoskeletal activity, processes intimately involved in the development and maintenance of fibrosis at the cellular and tissue levels [110]. Specifically, exogenous FGF2 resulted in a substantial downregulation of expression of the pro-fibrotic cytokine interleukin 6 (IL-6), a finding that has also been described elsewhere, though this activity appears to be context-dependent and/or cell type-specific [119–122]. Due to the data demonstrating that FGF2 can negatively regulate IL-6 and the well-established links between interleukin-6 in fibrosis, further discussion of this relationship is warranted.…”