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...

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Main Authors: Carla A Da Silva, Nelly Frossard
Format: Article
Language:English
Published: Fundação Oswaldo Cruz (FIOCRUZ) 2005-03-01
Series:Memorias do Instituto Oswaldo Cruz
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762005000900025
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author Carla A Da Silva
Nelly Frossard
author_facet Carla A Da Silva
Nelly Frossard
author_sort Carla A Da Silva
collection DOAJ
description 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.
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spelling doaj.art-12fa85afb5b148218d6e175498fc6a612023-09-02T16:25:12ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz0074-02761678-80602005-03-0110014515110.1590/S0074-02762005000900025Regulation of stem cell factor expression in inflammation and asthmaCarla A Da SilvaNelly FrossardStem 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762005000900025stem cell factorinflammationasthma
spellingShingle Carla A Da Silva
Nelly Frossard
Regulation of stem cell factor expression in inflammation and asthma
Memorias do Instituto Oswaldo Cruz
stem cell factor
inflammation
asthma
title Regulation of stem cell factor expression in inflammation and asthma
title_full Regulation of stem cell factor expression in inflammation and asthma
title_fullStr Regulation of stem cell factor expression in inflammation and asthma
title_full_unstemmed Regulation of stem cell factor expression in inflammation and asthma
title_short Regulation of stem cell factor expression in inflammation and asthma
title_sort regulation of stem cell factor expression in inflammation and asthma
topic stem cell factor
inflammation
asthma
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762005000900025
work_keys_str_mv AT carlaadasilva regulationofstemcellfactorexpressionininflammationandasthma
AT nellyfrossard regulationofstemcellfactorexpressionininflammationandasthma