uterine epithelial cells specifically induce interferon-stimulated genes in response to polyinosinic-polycytidylic acid independently of estradiol明确子宫上皮细胞诱导干扰素刺激基因独立polyinosinic-polycytidylic酸雌二醇的反应.pdfVIP

uterine epithelial cells specifically induce interferon-stimulated genes in response to polyinosinic-polycytidylic acid independently of estradiol明确子宫上皮细胞诱导干扰素刺激基因独立polyinosinic-polycytidylic酸雌二醇的反应.pdf

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uterine epithelial cells specifically induce interferon-stimulated genes in response to polyinosinic-polycytidylic acid independently of estradiol明确子宫上皮细胞诱导干扰素刺激基因独立polyinosinic-polycytidylic酸雌二醇的反应

Uterine Epithelial Cells Specifically Induce Interferon- Stimulated Genes in Response to Polyinosinic- Polycytidylic Acid Independently of Estradiol Mickey V. Patel*, Mimi Ghosh, John V. Fahey, Charles R. Wira Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire, United States of America Abstract Interferon b (IFNb) is an antiviral cytokine secreted in response to pathogenic exposure that creates a restrictive intracellular environment through the action of downstream interferon-stimulated genes (ISG). The objective of this study was to examine the expression of IFNb and ISG in both human uterine epithelial cells (UEC) and the ECC-1 uterine epithelial cell line and determine if expression changes with TLR stimulation and hormone exposure. Stimulation of primary uterine epithelial cells and ECC-1 cells with the TLR3 agonist poly (I:C) induced the mRNA expression of IFNb, MxA, OAS2 and PKR. Other TLR agonists including imiquimod and CpG had no effect on either IFNb or ISG expression. In contrast to ECC-1 cell responses which were slower, maximal IFNb upregulation in UEC occurred 3 hours post-stimulation and preceded the ISG response which peaked approximately 12 hours after poly (I:C) exposure. Unexpectedly, estradiol, either alone or prior to treatment with poly (I:C), had no effect on IFNb or ISG expression. Blockade of the IFN receptor abrogated the upregulation of MxA, OAS2 and PKR. Furthermore, neutralizing antibodies against IFNb partially inhibited the upregulation of all three ISG. Estradiol, directly and in the presence of poly (I:C) had no effect on IFNb and ISG expression. These results indicate that uterine epithelial cells are important sentinels of the innate immune system and demonstrate that uterine epithelial cells are capable of mounting a rapid IFN-mediated antiviral response that is independen

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