Department of Medicine , University of Alabama School of Medicine , Birmingham 35294 .
Am J Physiol 261 : L378-85 ( 1991)
Abstract
Growth factors produced by alveolar macrophages are thought to promote the fibroblast proliferation within interstitial spaces of fibrotic lungs .
This study investigated the possibility that the macrophage-produced growth factors might modulate the expression of basic fibroblast growth factor ( bFGF ) by lung fibroblasts .
To evaluate this question , bFGF gene expression and protein production were evaluated in normal adult human lung fibroblast cell lines .
Under normal culture conditions , the fibroblasts expressed the bFGF gene as two major transcripts ( 7.1 , 3.7 kb ) .
The addition of fetal calf serum ( FCS ) to serum-starved fibroblasts caused a 5- to 10-fold increase in bFGF expression .
Steady-state bFGF expression was increased 108% by platelet-derived growth factor ( PDGF ) and 602% by transforming growth factor-beta ( TGF-beta ) .
Insulin-like growth factor-1 had no significant effect on bFGF expression .
Nuclear runoff studies demonstrated that both PDGF and TGF-beta increased the relative rates of bFGF transcription in the fibroblasts .
Western blot analysis of lysates from fibroblasts treated with either PDGF or TGF-beta had no detectable increase in bFGF protein above unstimulated controls .
However , the simultaneous addition of PDGF and TGF-beta , or FCS , produced a marked increase in bFGF .
These experiments show that two growth factors present in the alveolar airspace compartment of fibrotic lungs can promote the expression of bFGF within lung fibroblasts .
Gene Symbols
Chemical Identifiers ( Names)
Research Department , Ciba-Geigy Ltd. , Basel , Switzerland .
FEBS Lett 291 : 249-52 ( 1991)
Abstract
Treatment of rat mesangial cells with interleukin 1 beta ( IL-1 beta ) and forskolin greatly enhanced the expression of group II phospholipase A2 ( PLA2 ) mRNA , with subsequent increased synthesis and secretion of PLA2 , as detected by PLA2 activity measurements and immunoprecipitation of culture media of [ 35S]methionine-labelled mesangial cells .
PDGF-BB dose-dependently suppressed the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA , as well as PLA2 synthesis and secretion .
In contrast , PDGF-AA had no inhibitory effect .
The tyrosine kinase inhibitor genistein dose-dependently antagonized the inhibitory effect of PDGF-BB on IL-1 beta-stimulated PLA2 secretion , thus suggesting that tyrosine phosphorylation may be required for PDGF-BB inhibition of PLA2 gene expression in mesangial cells .