Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix

Lyndsey R. Buckner, Danny J. Schust, Jian Ding, Takeshi Nagamatsu, Wandy Beatty, Theresa L. Chang, Sheila J. Greene, Maria E. Lewis, Bernardo Ruiz, Stacey L. Holman, Rae Ann Spagnuolo, Richard Pyles, Alison J. Quayle

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The endocervix in the female reproductive tract (FRT) is susceptible to sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Endocervical epithelial cells in vivo make innate immune mediators that likely aid in the protection from these pathogens. In vitro studies to investigate the innate epithelial cell immune response to endocervical pathogens have been hindered by the paucity of human endocervix-derived epithelial cell lines that display the differentiation proteins and functional characteristics of their site of origin. We have established an immortalized epithelial cell line (A2EN) derived from an endocervical tissue explant that can be polarized to exhibit distinct apical and basolateral membrane domains. Polarized A2EN cells secrete mucus at their apical surface, and express MUC5B, a mucin specific to the endocervix. Polarized A2EN cells also express hormone receptors that respond appropriately to female steroid hormones. Polarized A2EN cells can be stimulated with the toll-like receptor 3 agonist, polyI:C, to express anti-microbial peptides (AMPs) as well as pro-inflammatory cytokines and chemokines. Cytokines and chemokines are also differentially secreted depending on the hormone milieu in which the cells are exposed. We conclude that polarized A2EN cells maintain distinctive phenotypic and functional characteristics of the epithelial cells found in the endocervix and, hence, could provide a useful, new in vitro model system for investigations on the role of endogenous and exogenous factors that regulate endocervical epithelial cell immunity including studies on sexually transmitted infections and topical microbicides.

Original languageEnglish (US)
Pages (from-to)8-20
Number of pages13
JournalJournal of Reproductive Immunology
Volume92
Issue number1-2
DOIs
StatePublished - Dec 2011

Fingerprint

Epithelial Cells
Hormones
Chemokines
Toll-Like Receptor 3
Cytokines
Cell Line
Local Anti-Infective Agents
Neisseria gonorrhoeae
Chlamydia trachomatis
Mucins
Mucus
Sexually Transmitted Diseases
Immunity
Steroids
Peptides
Membranes
Proteins
In Vitro Techniques

Keywords

  • Anti-microbial peptide
  • Cytokine
  • Female genital tract
  • Hormone

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix. / Buckner, Lyndsey R.; Schust, Danny J.; Ding, Jian; Nagamatsu, Takeshi; Beatty, Wandy; Chang, Theresa L.; Greene, Sheila J.; Lewis, Maria E.; Ruiz, Bernardo; Holman, Stacey L.; Spagnuolo, Rae Ann; Pyles, Richard; Quayle, Alison J.

In: Journal of Reproductive Immunology, Vol. 92, No. 1-2, 12.2011, p. 8-20.

Research output: Contribution to journalArticle

Buckner, LR, Schust, DJ, Ding, J, Nagamatsu, T, Beatty, W, Chang, TL, Greene, SJ, Lewis, ME, Ruiz, B, Holman, SL, Spagnuolo, RA, Pyles, R & Quayle, AJ 2011, 'Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix', Journal of Reproductive Immunology, vol. 92, no. 1-2, pp. 8-20. https://doi.org/10.1016/j.jri.2011.08.002
Buckner, Lyndsey R. ; Schust, Danny J. ; Ding, Jian ; Nagamatsu, Takeshi ; Beatty, Wandy ; Chang, Theresa L. ; Greene, Sheila J. ; Lewis, Maria E. ; Ruiz, Bernardo ; Holman, Stacey L. ; Spagnuolo, Rae Ann ; Pyles, Richard ; Quayle, Alison J. / Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix. In: Journal of Reproductive Immunology. 2011 ; Vol. 92, No. 1-2. pp. 8-20.
@article{001881fa2faa4bc59f0b8f11216380d9,
title = "Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix",
abstract = "The endocervix in the female reproductive tract (FRT) is susceptible to sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Endocervical epithelial cells in vivo make innate immune mediators that likely aid in the protection from these pathogens. In vitro studies to investigate the innate epithelial cell immune response to endocervical pathogens have been hindered by the paucity of human endocervix-derived epithelial cell lines that display the differentiation proteins and functional characteristics of their site of origin. We have established an immortalized epithelial cell line (A2EN) derived from an endocervical tissue explant that can be polarized to exhibit distinct apical and basolateral membrane domains. Polarized A2EN cells secrete mucus at their apical surface, and express MUC5B, a mucin specific to the endocervix. Polarized A2EN cells also express hormone receptors that respond appropriately to female steroid hormones. Polarized A2EN cells can be stimulated with the toll-like receptor 3 agonist, polyI:C, to express anti-microbial peptides (AMPs) as well as pro-inflammatory cytokines and chemokines. Cytokines and chemokines are also differentially secreted depending on the hormone milieu in which the cells are exposed. We conclude that polarized A2EN cells maintain distinctive phenotypic and functional characteristics of the epithelial cells found in the endocervix and, hence, could provide a useful, new in vitro model system for investigations on the role of endogenous and exogenous factors that regulate endocervical epithelial cell immunity including studies on sexually transmitted infections and topical microbicides.",
keywords = "Anti-microbial peptide, Cytokine, Female genital tract, Hormone",
author = "Buckner, {Lyndsey R.} and Schust, {Danny J.} and Jian Ding and Takeshi Nagamatsu and Wandy Beatty and Chang, {Theresa L.} and Greene, {Sheila J.} and Lewis, {Maria E.} and Bernardo Ruiz and Holman, {Stacey L.} and Spagnuolo, {Rae Ann} and Richard Pyles and Quayle, {Alison J.}",
year = "2011",
month = "12",
doi = "10.1016/j.jri.2011.08.002",
language = "English (US)",
volume = "92",
pages = "8--20",
journal = "Journal of Reproductive Immunology",
issn = "0165-0378",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix

AU - Buckner, Lyndsey R.

AU - Schust, Danny J.

AU - Ding, Jian

AU - Nagamatsu, Takeshi

AU - Beatty, Wandy

AU - Chang, Theresa L.

AU - Greene, Sheila J.

AU - Lewis, Maria E.

AU - Ruiz, Bernardo

AU - Holman, Stacey L.

AU - Spagnuolo, Rae Ann

AU - Pyles, Richard

AU - Quayle, Alison J.

PY - 2011/12

Y1 - 2011/12

N2 - The endocervix in the female reproductive tract (FRT) is susceptible to sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Endocervical epithelial cells in vivo make innate immune mediators that likely aid in the protection from these pathogens. In vitro studies to investigate the innate epithelial cell immune response to endocervical pathogens have been hindered by the paucity of human endocervix-derived epithelial cell lines that display the differentiation proteins and functional characteristics of their site of origin. We have established an immortalized epithelial cell line (A2EN) derived from an endocervical tissue explant that can be polarized to exhibit distinct apical and basolateral membrane domains. Polarized A2EN cells secrete mucus at their apical surface, and express MUC5B, a mucin specific to the endocervix. Polarized A2EN cells also express hormone receptors that respond appropriately to female steroid hormones. Polarized A2EN cells can be stimulated with the toll-like receptor 3 agonist, polyI:C, to express anti-microbial peptides (AMPs) as well as pro-inflammatory cytokines and chemokines. Cytokines and chemokines are also differentially secreted depending on the hormone milieu in which the cells are exposed. We conclude that polarized A2EN cells maintain distinctive phenotypic and functional characteristics of the epithelial cells found in the endocervix and, hence, could provide a useful, new in vitro model system for investigations on the role of endogenous and exogenous factors that regulate endocervical epithelial cell immunity including studies on sexually transmitted infections and topical microbicides.

AB - The endocervix in the female reproductive tract (FRT) is susceptible to sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Endocervical epithelial cells in vivo make innate immune mediators that likely aid in the protection from these pathogens. In vitro studies to investigate the innate epithelial cell immune response to endocervical pathogens have been hindered by the paucity of human endocervix-derived epithelial cell lines that display the differentiation proteins and functional characteristics of their site of origin. We have established an immortalized epithelial cell line (A2EN) derived from an endocervical tissue explant that can be polarized to exhibit distinct apical and basolateral membrane domains. Polarized A2EN cells secrete mucus at their apical surface, and express MUC5B, a mucin specific to the endocervix. Polarized A2EN cells also express hormone receptors that respond appropriately to female steroid hormones. Polarized A2EN cells can be stimulated with the toll-like receptor 3 agonist, polyI:C, to express anti-microbial peptides (AMPs) as well as pro-inflammatory cytokines and chemokines. Cytokines and chemokines are also differentially secreted depending on the hormone milieu in which the cells are exposed. We conclude that polarized A2EN cells maintain distinctive phenotypic and functional characteristics of the epithelial cells found in the endocervix and, hence, could provide a useful, new in vitro model system for investigations on the role of endogenous and exogenous factors that regulate endocervical epithelial cell immunity including studies on sexually transmitted infections and topical microbicides.

KW - Anti-microbial peptide

KW - Cytokine

KW - Female genital tract

KW - Hormone

UR - http://www.scopus.com/inward/record.url?scp=81555198357&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81555198357&partnerID=8YFLogxK

U2 - 10.1016/j.jri.2011.08.002

DO - 10.1016/j.jri.2011.08.002

M3 - Article

VL - 92

SP - 8

EP - 20

JO - Journal of Reproductive Immunology

JF - Journal of Reproductive Immunology

SN - 0165-0378

IS - 1-2

ER -