Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells

Abstract Interferonε (IFNε) is a unique type I IFN that has distinct functions from IFNα/β. IFNε is constitutively expressed at mucosal tissues, including the female genital mucosa, and is reported to be modulated by estrogen and seminal plasma. However, its regulation by cytokines, including TNFα,...

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Main Authors: Jennifer Couret, Carley Tasker, Jaeha Kim, Tiina Sihvonen, Saahil Fruitwala, Alison J. Quayle, Pierre Lespinasse, Debra S. Heller, Theresa L. Chang
Format: Article
Language:English
Published: BMC 2017-11-01
Series:Cell & Bioscience
Online Access:http://link.springer.com/article/10.1186/s13578-017-0185-z
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author Jennifer Couret
Carley Tasker
Jaeha Kim
Tiina Sihvonen
Saahil Fruitwala
Alison J. Quayle
Pierre Lespinasse
Debra S. Heller
Theresa L. Chang
author_facet Jennifer Couret
Carley Tasker
Jaeha Kim
Tiina Sihvonen
Saahil Fruitwala
Alison J. Quayle
Pierre Lespinasse
Debra S. Heller
Theresa L. Chang
author_sort Jennifer Couret
collection DOAJ
description Abstract Interferonε (IFNε) is a unique type I IFN that has distinct functions from IFNα/β. IFNε is constitutively expressed at mucosal tissues, including the female genital mucosa, and is reported to be modulated by estrogen and seminal plasma. However, its regulation by cytokines, including TNFα, IL-1β, IL-6, IL-8, IL-17, IL-22 and IFNα, which are commonly present in the female genital mucosa, is not well documented in freshly isolated primary cervical cells from tissues. We determined the effect of these cytokines on gene expression of type I IFNs in an immortalized endocervical epithelial cell line (A2EN) and in primary cervical epithelial cells. Several pro-inflammatory cytokines were found to induce IFNε, and TNFα induced the strongest response in both cell types. Pretreatment of cells with the IκB inhibitor, which blocks the NF-κB pathway, suppressed TNFα-mediated IFNε gene induction and promoter activation. Expression of IFNα, IFNβ, and IFNε was differentially regulated in response to various cytokines. Taken together, our results show that regulation of these IFNs depends on cell type, cytokine concentration, and incubation time, highlighting the complexity of the cytokine network in the cervical epithelium.
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spelling doaj.art-fd1e9544b8a642fa80433946ff68cbdd2022-12-22T02:20:01ZengBMCCell & Bioscience2045-37012017-11-01711610.1186/s13578-017-0185-zDifferential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cellsJennifer Couret0Carley Tasker1Jaeha Kim2Tiina Sihvonen3Saahil Fruitwala4Alison J. Quayle5Pierre Lespinasse6Debra S. Heller7Theresa L. Chang8Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New JerseyDepartment of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New JerseyPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New JerseyPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New JerseyPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New JerseyDepartment of Microbiology, Immunology and Parasitology, Louisiana State University Health Science CenterDepartment of Obstetrics, Gynecology & Women’s Health, New Jersey Medical School, Rutgers, The State University of New JerseyDepartment of Obstetrics, Gynecology & Women’s Health, New Jersey Medical School, Rutgers, The State University of New JerseyPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New JerseyAbstract Interferonε (IFNε) is a unique type I IFN that has distinct functions from IFNα/β. IFNε is constitutively expressed at mucosal tissues, including the female genital mucosa, and is reported to be modulated by estrogen and seminal plasma. However, its regulation by cytokines, including TNFα, IL-1β, IL-6, IL-8, IL-17, IL-22 and IFNα, which are commonly present in the female genital mucosa, is not well documented in freshly isolated primary cervical cells from tissues. We determined the effect of these cytokines on gene expression of type I IFNs in an immortalized endocervical epithelial cell line (A2EN) and in primary cervical epithelial cells. Several pro-inflammatory cytokines were found to induce IFNε, and TNFα induced the strongest response in both cell types. Pretreatment of cells with the IκB inhibitor, which blocks the NF-κB pathway, suppressed TNFα-mediated IFNε gene induction and promoter activation. Expression of IFNα, IFNβ, and IFNε was differentially regulated in response to various cytokines. Taken together, our results show that regulation of these IFNs depends on cell type, cytokine concentration, and incubation time, highlighting the complexity of the cytokine network in the cervical epithelium.http://link.springer.com/article/10.1186/s13578-017-0185-z
spellingShingle Jennifer Couret
Carley Tasker
Jaeha Kim
Tiina Sihvonen
Saahil Fruitwala
Alison J. Quayle
Pierre Lespinasse
Debra S. Heller
Theresa L. Chang
Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells
Cell & Bioscience
title Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells
title_full Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells
title_fullStr Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells
title_full_unstemmed Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells
title_short Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells
title_sort differential regulation of ifnα ifnβ and ifnε gene expression in human cervical epithelial cells
url http://link.springer.com/article/10.1186/s13578-017-0185-z
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