Estradiol-regulated innate antiviral responses of human endometrial stromal fibroblasts
| Autor: | Zheng Shen, Richard M. Rossoll, Mickey V. Patel, Charles R. Wira |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Immunology Biology Article 03 medical and health sciences Endometrium Immune system Downregulation and upregulation Antigen Immunity Immunology and Allergy Humans Secretion Antigens Viral Cells Cultured Aged Aged 80 and over Innate immune system Estradiol Obstetrics and Gynecology Fibroblasts Middle Aged Molecular biology Immunity Innate CCL20 030104 developmental biology Poly I-C Reproductive Medicine Virus Diseases Interferon Type I Female Signal transduction Stromal Cells Transcriptome Signal Transduction |
| Popis: | PROBLEM: The contribution of fibroblasts to innate immune protection of the human female reproductive tract (FRT) against viral pathogens is relatively unknown. METHOD OF STUDY: Endometrial (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 (E(2)), with gene expression measured by real-time RT-PCR and protein secretion by ELISA. RESULTS: Poly (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. E(2) inhibited the poly (I:C)-induced upregulation of MxA and OAS2 in EM fibroblasts, but not Cx or ECx fibroblasts. E(2) upregulated 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 or E2-treated fibroblasts significantly reduced HIV infection of CD4+ T cells. CONCLUSIONS: Stromal 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 to E(2), capable of initiating an antiviral response against viral pathogens, and may play a role in preventing HIV infection of CD4+ T cells. |
| Databáze: | OpenAIRE |
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