IL-36 gamma 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-36 gamma 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-36 gamma and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36 gamma in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36 gamma treatment resulted in self amplification of IL-36 gamma 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-36 gamma are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36 gamma 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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/617371 |
| Date | 17 June 2016 |
| Creators | Winkle, Sean M., Throop, Andrea L., Herbst-Kralovetz, Melissa M. |
| Contributors | Univ Arizona, Coll Med Phoenix, Dept Basic Med Sci |
| Publisher | FRONTIERS MEDIA SA |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | Copyright © 2016 Winkle, Throop and Herbst-Kralovetz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). |
| Relation | http://journal.frontiersin.org/Article/10.3389/fmicb.2016.00955/abstract |
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