Alteration of glucocorticoid receptors and exacerbation of inflammation during lytic cytomegalovirus infection in THP-1 cells.

Alteration of glucocorticoid receptors and exacerbation of inflammation during lytic cytomegalovirus infection in THP-1 cells.
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THP-1 细胞中裂解性巨细胞病毒感染期间糖皮质激素受体的改变和炎症加剧

DOI:
10.1002/2211-5463.12334
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发表时间:
2017-12
期刊:
影响因子:
2.6
通讯作者:
Qian J
Qian J
中科院分区:
生物学4区
文献类型:
--
作者:
Wang S;Dou Y;Yang H;Ni A;Zhang R;Qian J

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巨细胞病毒(CMV)感染与溃疡性结肠炎(UC)中的糖皮质激素抵抗相关,并可能加重病程。然而,潜在的致病性仍不清楚。本研究的目的是探索人单核细胞系THP-1中CMV潜伏期和裂解性感染期间可能的潜在机制。建立CMV潜伏感染和激活感染细胞模型。我们进行了真实的实时PCR和蛋白质印迹法,以检查糖皮质激素受体(GR)在CMV潜伏期和激活期间的变化。通过ELISA检测促炎和抗炎细胞因子。UV灭活CMV感染后,还检查了GR和细胞因子。再激活组GRs表达增强。CMV再激活组GR β/α比值升高和GRα磷酸化可能解释激素难治性反应。在CMV溶解性感染期间,促炎细胞因子IL-6和TNF-α显著升高,抗炎细胞因子IL-5降低,这可能加重UC。GR和细胞因子在UV灭活的CMV感染组中没有变化。GR数量和功能的变化可能是CMV再激活中糖皮质激素抵抗的原因。促炎细胞因子和抗炎细胞因子的失衡可能与严重炎症有关。
Cytomegalovirus (CMV) infection is associated with glucocorticoid resistance in ulcerative colitis (UC) and may exacerbate the disease course. However, the underlying pathogenicity remains unclear. The aim of this study was to explore possible underlying mechanisms during CMV latency and lytic infection in the human mononuclear cell line THP‐1. Latent and activated CMV infection cell models were established. We performed real‐time PCR and western blotting to examine changes in glucocorticoid receptors (GRs) during CMV latency and activation. Pro‐inflammatory and anti‐inflammatory cytokines were detected by ELISA. After UV‐inactivated CMV infection, GRs and cytokines were also examined. The expression of GRs was elevated in the reactivation group. An increased ratio of GR β/α and phosphorylation of GRα in the CMV reactivation group may explain refractory response to steroids. During CMV lytic infection, pro‐inflammatory cytokines IL‐6 and TNF‐α increased remarkably and anti‐inflammatory cytokine IL‐5 decreased, which may exacerbate UC. GR and cytokines were unchanged in the UV‐inactivated CMV infection group. Changes in the number and function of GRs may account for glucocorticoid resistance in CMV reactivation. The imbalance of pro‐ and anti‐inflammatory cytokines may be related to severe inflammation.
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