IL-36γ augments host defense and immune responses in human female reproductive tract epithelial cells

Sean M. Winkle, Andrea L. Throop, Melissa Herbst-Kralovetz

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

IL-36γ is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36γ in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36γ and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36γ in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36γ treatment resulted in self-amplification of IL-36γ and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36γ are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36γ is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.

Original languageEnglish (US)
Article number955
JournalFrontiers in Microbiology
Volume7
Issue numberJUN
DOIs
StatePublished - 2016

Fingerprint

Epithelial Cells
Cytokines
Flagellin
Poly I-C
Interleukin-1
Viruses
Gene Expression
Lung
Skin

Keywords

  • Antimicrobial peptides
  • Human epithelial cells
  • IL-1 family
  • IL-36 receptor
  • IL-36γ
  • Inflammatory mediators
  • Innate immunity
  • Microbial products

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

IL-36γ augments host defense and immune responses in human female reproductive tract epithelial cells. / Winkle, Sean M.; Throop, Andrea L.; Herbst-Kralovetz, Melissa.

In: Frontiers in Microbiology, Vol. 7, No. JUN, 955, 2016.

Research output: Contribution to journalArticle

@article{a51e4104e2964e088526b5c1a89bdd27,
title = "IL-36γ augments host defense and immune responses in human female reproductive tract epithelial cells",
abstract = "IL-36γ is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36γ in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36γ and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36γ in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36γ treatment resulted in self-amplification of IL-36γ and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36γ are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36γ is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.",
keywords = "Antimicrobial peptides, Human epithelial cells, IL-1 family, IL-36 receptor, IL-36γ, Inflammatory mediators, Innate immunity, Microbial products",
author = "Winkle, {Sean M.} and Throop, {Andrea L.} and Melissa Herbst-Kralovetz",
year = "2016",
doi = "10.3389/fmicb.2016.00955",
language = "English (US)",
volume = "7",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S. A.",
number = "JUN",

}

TY - JOUR

T1 - IL-36γ augments host defense and immune responses in human female reproductive tract epithelial cells

AU - Winkle, Sean M.

AU - Throop, Andrea L.

AU - Herbst-Kralovetz, Melissa

PY - 2016

Y1 - 2016

N2 - IL-36γ is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36γ in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36γ and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36γ in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36γ treatment resulted in self-amplification of IL-36γ and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36γ are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36γ is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.

AB - IL-36γ is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36γ in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36γ and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36γ in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36γ treatment resulted in self-amplification of IL-36γ and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36γ are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36γ is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.

KW - Antimicrobial peptides

KW - Human epithelial cells

KW - IL-1 family

KW - IL-36 receptor

KW - IL-36γ

KW - Inflammatory mediators

KW - Innate immunity

KW - Microbial products

UR - http://www.scopus.com/inward/record.url?scp=84980022416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84980022416&partnerID=8YFLogxK

U2 - 10.3389/fmicb.2016.00955

DO - 10.3389/fmicb.2016.00955

M3 - Article

AN - SCOPUS:84980022416

VL - 7

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

IS - JUN

M1 - 955

ER -