title: Immunomodulatory effects of dexamethasone on gene expression of cytokine and stress hormone receptors in peripheral blood mononuclear cells.
abstract: Glucocorticoid (GC) such as cortisol in humans is a major stress hormone and can influence immunomodulation through various mechanisms including impact on regulatory T-cell (RTC) elements and changes in Th1/Th2 cytokine balance. In this study, we sought to determine the immunomodulatory effects of GC equivalent dexamethasone (DEX) at various concentrations (10(-7), 10(-8), and 10(-9) M) on gene expression of RTC, cytokine receptors and stress hormone receptors from normal human peripheral blood mononuclear cells (PBMC) in an in vitro stress model in 24 h (acute stress) vs 11-day (chronic stress) cultures. Results revealed that the mRNA of forkhead box P3 (FoxP3) was significantly decreased at 24 h with 10(-7) and 10(-8) M DEX. After 11 days, FoxP3 expression in the 10(-8) M DEX cultures had returned to baseline but was still down-regulated with 10(-7) M DEX. GC receptor (GR) mRNA decreased and β2 adrenergic receptor (β 2AR) mRNA increased significantly after 24 h exposure to DEX. These changes had returned to baseline in the 11-day cultures. The IFN-γR/IL-4R ratio, an alternative marker for Th1/Th2 balance, was significantly increased at 24 h and decreased after 11-day cultures with 10(-7) and 10(-8) M DEX compared to control cultures. These findings further contribute to our understanding of the mechanisms associated with the effects of acute vs. chronic stress on normal immune balance.
authors: Laboratory of Behavioral Immunology Research, Division of Clinical Immunology and Allergy, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: lxiang@umc.edu.
authors: Lianbin
authors: L
authors: Xiang
authors: Gailen D
authors: GD
authors: Marshall
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics; D055815:Young Adult; D000096743:Interferon gamma Receptor
chemical_list: D003907:Dexamethasone; D051858:Forkhead Transcription Factors; D007155:Immunologic Factors; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid; D017471:Receptors, Interferon; D019948:Receptors, Interleukin-4; D000096743:Interferon gamma Receptor; C418974:FOXP3 protein, human
keywords: Cytokines; Dexamethasone; Gene expression; Glucocorticoids; Immunomodulation; Receptor