Stem cell factor (SCF) is a major
mast cell growth factor, which could be involved in the local increase of mast cell number in the asthmatic airways. In vivo, SCF expression increases in asthmatic patients and this is reversed
after treatment with
glucocorticoids. In vitro in human lung fibroblasts in culture, IL-1beta, a pro-inflammatory
cytokine, confirms this increased SCF
mRNA and
protein expression implying the MAP
kinases p38 and ERK1/2 very early post-treatment, and
glucocorticoids confirm this decrease. Surprisingly,
glucocorticoids potentiate the IL-1beta-enhanced SCF expression at short term treatment, implying increased SCF mRNA stability and SCF gene transcription rate. This potentiation involves p38 and ERK1/2. Transfection experiments with the SCF promoter including intron1 also confirm this increase and decrease of SCF expression by IL-1beta and
glucocorticoids, and the potentiation by
glucocorticoids of the IL-1beta-induced SCF expression. Deletion of the GRE or kappaB sites abolishes this potentiation, and the effect of IL-1beta or
glucocorticoids alone.
DNA binding of GR and
NF-kappaB are also demonstrated for these effects. In conclusion, this review concerns new mechanisms of regulation of SCF expression in
inflammation that could lead to potential therapeutic strategy allowing to control mast cell number in the asthmatic airways.