Glucocorticoid receptor BclI polymorphism associates with immunomodulatory response to stress hormone in human peripheral blood mononuclear cells

Abstract

Glucocorticoid receptor (GR) variants have been found to be associated with stress-related disorders. Our previous in vivo study revealed that the CC allele of GR BclI single-nucleotide polymorphism (SNP) was more common in the high-stress group, which had lower levels of both regulatory T cells (Treg) and Th1 cytokine. The current study was to investigate the associations between GR BclI polymorphism and immunomodulatory response to stress hormone in vitro in human peripheral blood mononuclear cells (PBMC). Blood samples were collected from 18 normal volunteers including 9 subjects with BclI polymorphism GG allele and 9 with wild-type (WT) CC allele. PBMC were cultured with 10(-8) m dexamethasone (DEX), which mimics the plasma cortisol level observed during periods of psychological stress for 24 h and 11 days. Gene expressions of transcription factors, stress hormone and cytokine receptors were analysed by real-time RT-PCR. FoxP3 mRNA was significantly altered in the BclI WT (decreased at 24 h and increased at 11 days) but not in the GG allele. GR mRNA was up-regulated at 24 h and down-regulated at 11 days in CC alleles (P < 0.01 and P < 0.05), rather than in GG alleles. The expression of β-2 adrenergic receptor (β2AR) was increased at 24 h in both CC and GG alleles (P < 0.01 and P < 0.001), but decreased significantly at 11 days in only GG alleles. Expression of T-bet and GATA-3 was altered simultaneously in 24-h culture with DEX from both groups. The BclI polymorphism of GR identifies different immunomodulatory responses to corticosteroids, which may explain, at least in part, the variability in individual sensitivity to stressors.