Premium
Effects of glucocorticoids on STAT4 activation in human T cells are stimulus‐dependent
Author(s) -
Fahey Angela J.,
Robins R. Adrian,
Kindle Karin B.,
Heery David M.,
Constantinescu Cris S.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605296
Subject(s) - biology , stimulus (psychology) , microbiology and biotechnology , neuroscience , biophysics , cognitive psychology , psychology
Glucocorticoids affect the immune system by a number of mechanisms, including modulation of cytokine production in lymphocytes. Glucocorticoids suppress T helper cell type 1 immune responses by decreasing the ability of T cells to respond to interleukin (IL)‐12, a major inducer of interferon (IFN)‐γ. IFN‐β increases the expression of the anti‐inflammatory cytokine IL‐10 and suppresses IL‐12. Signaling pathways through IFN‐β and the IL‐12 receptor (IL‐12R) involve activation by phosphorylation of signal transducer and activator of transcription 4 (STAT4). Our aim was to investigate the effects of dexamethasone on STAT4 activation by IFN‐β and IL‐12 in human T cell blasts. We report that dexamethasone decreases IL‐12‐induced STAT4 phosphorylation and IFN‐γ production and enhances IFN‐β‐induced STAT4 activation and IL‐10 production. These effects are associated with a down‐regulation of IL‐12Rβ1 expression but an up‐regulation of IFN‐βR. These results indicate that the effect of glucocorticoids on the STAT4 signaling pathway depends on the stimulus activating that pathway.