ABSTRACT
INTRODUCTION: Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppressive effects in previous studies. In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. RESULTS: The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10â»7M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. CONCLUSION: In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction.
ABSTRACT
Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Conflicting data are reported regarding pro- and anti-inflammatory properties of estradiol. This study was designed to clarify whether estradiol may contribute to enhanced T helper (Th) 17-associated cytokines production by peripheral blood mononuclear cells (PBMC) in asthmatic patients and healthy individuals. PBMCs from patients with asthma and healthy donors were cultured with 17-ß estradiol (E2) and phytohemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure IL-6, IL-17, IL-23 and TGF-ß. We observed a significant increased IL-17, IL-23 and TGF-ß expression in PBMCs of patients compared to the healthy individuals. In addition, our findings indicated that IL-6 and IL-17 expressions in PBMCs were induced, following E2 treatment. Our results identified an impact of E2 in stimulation of Th17 phenotype, and upon hormonal oscillations and hormone replacement therapy (HRT), asthma inflammation may be mediated by Th17-associated cytokines.
