Estradiol-regulated innate antiviral responses of human endometrial stromal fibroblasts.
Estradiol-regulated innate antiviral responses of human endometrial stromal fibroblasts.
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雌二醇调节人子宫内膜基质成纤维细胞的先天抗病毒反应。
DOI：
10.1111/aji.13042
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Wira,CharlesR
中科院分区：
文献类型：
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作者：
Patel,MickeyV;Shen,Zheng;Rossoll,RichardM;Wira,CharlesR
ProblemThe贡献的成纤维细胞的先天性免疫保护的人类女性生殖道（FRT）对病毒pathogenes.Method研究子宫内膜（EM），子宫颈内（Cx）和子宫颈外（ECx）成纤维细胞分离子宫切除术患者和生长在体外。在存在或不存在性激素雌二醇（E2）的情况下，用病毒模拟物poly（I：C）处理成纤维细胞，通过真实的-time RT-PCR和ELISA测定蛋白分泌的基因表达。ResultsPoly（I：C）诱导干扰素刺激基因（ISG）MxA，OAS 2和APOBEC 3G的表达，以及来自所有三个部位的成纤维细胞的细胞因子MCP-1，IL-8，IL-6，CCL 20，IFNβ和RANTES。E2可抑制poly（I：C）诱导的EM成纤维细胞中MxA和OAS 2的上调，但对Cx或ECx成纤维细胞无影响; E2可上调EM成纤维细胞的SDF-1α，但对其他细胞因子的分泌无影响。条件培养基（CM）从聚（I：C）处理或E2处理的成纤维细胞显着减少HIV感染的CD 4 + T cells.ConclusionStromal成纤维细胞代表的先天免疫保护水平，对病毒病原体在FRT超越所看到的上皮细胞和免疫细胞。我们的研究结果表明，成纤维细胞FRT是选择性响应于E2，能够启动抗病毒病原体的抗病毒反应，并可能在预防HIV感染的CD 4 + T细胞中发挥作用。
ProblemThe contribution of fibroblasts to innate immune protection of the human female reproductive tract (FRT) against viral pathogens is relatively unknown.Method of StudyEndometrial (EM), endocervical (Cx) and ectocervical (ECx) fibroblasts were isolated from hysterectomy patients and grown in vitro. Fibroblasts were treated with the viral mimic poly (I:C) in the presence or absence of the sex hormone estradiol (E2), with gene expression measured by real‐time RT‐PCR and protein secretion by ELISA.ResultsPoly (I:C) induced the expression of the interferon‐stimulated genes (ISG) MxA, OAS2 and APOBEC3G, and the cytokines MCP‐1, IL‐8, IL‐6, CCL20, IFNβ and RANTES by fibroblasts from all three sites. ISG upregulation was dependent upon Type I IFN signaling.E2inhibited the poly (I:C)‐induced upregulation of MxA and OAS2 in EM fibroblasts, but not Cx or ECx fibroblasts.E2upregulated SDF‐1α by EM fibroblasts but had no effect on secretion of other cytokines either alone or in the presence of poly (I:C). Conditioned media (CM) from poly (I:C)‐treated orE2‐treated fibroblasts significantly reduced HIV infection of CD4+ T cells.ConclusionStromal fibroblasts represent a level of innate immune protection against viral pathogens in the FRT beyond that seen with epithelial cells and immune cells. Our findings indicate that fibroblasts FRT are selectively responsive toE2, capable of initiating an antiviral response against viral pathogens and may play a role in preventing HIV infection of CD4+ T cells.