Regulation of stem cell factor expression in inflammation and asthma.
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.
Da Silva
Carla A
CA
Faculté de Pharmacie, Université Louis Pasteur, 67401 Illkirch cedex, France.
Frossard
Nelly
N
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007375:Interleukin-1; D019089:Stem Cell Factor