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Inhibition by glucocorticoids of the interleukin‐1β‐enhanced expression of the mast cell growth factor SCF
Author(s) -
Silva Carla Alexandra Da,
Kassel Olivier,
Mathieu Eric,
Massard Gilbert,
Gasser Bernard,
Frossard Nelly
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704617
Subject(s) - stem cell factor , glucocorticoid , cytokine , mast cell , medicine , cell culture , messenger rna , glucocorticoid receptor , budesonide , endocrinology , microbiology and biotechnology , biology , chemistry , haematopoiesis , immunology , corticosteroid , stem cell , biochemistry , genetics , gene
Stem cell factor (SCF) is a major mast cell growth factor that promotes differentiation and chemotaxis of mast cells and inhibits their apoptosis. We evaluated the effect of interleukin (IL)‐1β, a major pro‐inflammatory cytokine, on the constitutive expression of SCF and studied the effects of two glucocorticoids, budesonide and dexamethasone, on the IL‐1β‐enhanced SCF expression. Human lung fibroblasts in culture were serum‐starved for 48 h and treated with IL‐1β, budesonide and/or RU486. SCF cDNA was quantified after total RNA reverse transcription by on‐line fluorescent polymerase chain reaction. SCF protein was quantified by ELISA. IL‐1β induced an increase in SCF mRNA (+91% at 2.5 h) and protein production (+32%) by human lung fibroblasts in culture ( P <0.001). Budesonide inhibited IL‐1β‐induced SCF mRNA expression (−68%) at 2.5 h and even more so at 10 h (−192%) ( P <0.001). The expression of SCF protein also decreased by 3.5‐fold at 10 h. Results were similar with dexamethasone. The glucocorticoid antagonist RU486 cancelled the effects induced by the glucocorticoids. Increased SCF mRNA levels were associated with increased stability of this mRNA as measured after treatment with actinomycin D (1.9‐fold at 2.5 h). Budesonide decreased this IL‐1β‐enhanced stability by about 1.5‐fold ( P <0.001). We conclude that in ‘inflammatory’ conditions, mimicked in vitro by IL‐1β, glucocorticoid treatment inhibits expression of the mast cell growth factor SCF. The reduced number and activation of mast cells observed in the bronchi of asthmatic patients treated by glucocorticoids may be due in part to this effect.British Journal of Pharmacology (2002) 135 , 1634–1640; doi: 10.1038/sj.bjp.0704617