Palizgir Mohammad Taghi, Akhtari Maryam, Mahmoudi Mahdi, Mostafaei Shayan, Rezaeimanesh Alireza, Akhlaghi Massoomeh, Shahram Farhad
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2017 Oct;16(5):418-424.
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days. Cells were then polarized to M1 macrophages by lipopolysaccharide (LPS) and interferon-γ (IFNγ) for 24h. Monocyte purity and macrophage markers expression were analyzed by flow cytometry. Analysis of AHR mRNA expression was performed by SYBR Green real-time PCR. Our results showed that AHR expression is significantly down-regulated in M1 macrophages compare to monocyte-derived macrophages. It was shown that both monocyte-derived macrophages and M1 macrophages from BD patients significantly express lower level of AHR mRNA compared to healthy individuals. Our results demonstrate an anti-inflammatory role for AHR in macrophages, which suggest that decreased AHR expression is associated with pro-inflammatory M1 macrophage and BD susceptibility.
芳烃受体（AHR）是一种配体激活的转录因子，它将环境刺激物与免疫系统联系起来。M1巨噬细胞是免疫系统的一部分，在白塞病（BD）发病机制中促成炎症反应。AHR对BD患者巨噬细胞的影响尚不清楚。在本研究中，我们比较了健康对照者与活动期BD患者中，单核细胞来源的巨噬细胞和M1巨噬细胞中AHR的mRNA表达。从10名健康对照者和10名活动期BD患者中分离出单核细胞，用巨噬细胞集落刺激因子（M-CSF）诱导分化为巨噬细胞，持续7天。然后用脂多糖（LPS）和干扰素-γ（IFNγ）将细胞极化为M1巨噬细胞，持续24小时。通过流式细胞术分析单核细胞纯度和巨噬细胞标志物表达。采用SYBR Green实时PCR法分析AHR mRNA表达。我们的结果显示，与单核细胞来源的巨噬细胞相比，M1巨噬细胞中AHR表达显著下调。结果表明，与健康个体相比，BD患者的单核细胞来源巨噬细胞和M1巨噬细胞中AHR mRNA表达水平均显著降低。我们的结果证明了AHR在巨噬细胞中的抗炎作用，这表明AHR表达降低与促炎M1巨噬细胞及BD易感性相关。
