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Transcription of stem cell factor (SCF) is potentiated by glucocorticoids and interleukin‐1β through concerted regulation of a GRE‐like and an NF‐κB response element
Author(s) -
Da Silva Carla Alexandra,
Heilbock Christine,
Kassel Olivier,
Frossard Nelly
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0136fje
Subject(s) - chromatin immunoprecipitation , transcription factor , stem cell factor , response element , promoter , glucocorticoid , microbiology and biotechnology , biology , nfkb1 , nf κb , chemistry , signal transduction , gene expression , stem cell , gene , immunology , biochemistry , haematopoiesis
Expression of stem cell factor SCF, a major mast cell growth factor, is potentiated shortly after co‐treatment with interleukin (IL)‐1β and glucocorticoids. SCF promoter contains a GRE‐like sequence and a putative κB site. We assessed the mechanisms of the regulation of SCF transcription in human lung fibroblasts in culture. Chromatin immunoprecipitation showed that co‐treatment with IL‐1β and the glucocorticoid budesonide increased the SCF promoter occupancy by NF‐κB and GR, as compared with IL‐1β and budesonide alone. In reporter gene assays, IL‐1β time‐dependently increased the promoter activity, which was abolished by either pre‐treatment with the MAP kinase inhibitors PD98059 (MEK) and SB203580 (p38), pre treatment with the NF‐κB inhibitor PDTC, or deletion of the κB site. Budesonide time‐ dependently decreased the promoter activity, an effect requiring the GRE‐like element. Co‐ treatment with IL‐1β and budesonide potentiated the promoter activity at 30 min, an effect blocked by PD98059 and SB203580, PDTC, or deletion of the κB or GRE‐like element. In conclusion, the GRE‐like sequence mediating the repression of SCF expression, thus acting as a negative‐responsive element, is turned into a positive element in an NF‐κB site‐dependent manner, indicating a concerted action of these two regulatory elements in the potentiation of SCF gene expression.