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BOR - Papers in Press, published online ahead of print December 1, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.035618
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Submitted August 23, 2004
Returned for revision September 20, 2004
Accepted October 19, 2004

Female Reproductive Tract


Hepatocyte Growth Factor Regulation of Uterine Epithelial Cell Transepithelial Resistance and Tumor Necrosis Factor {alpha} Release In Culture

Katherine S. Grant-Tschudy and Charles R. Wira *

* To whom correspondence should be addressed. E-mail: charles.r.wira{at}dartmouth.edu.

Abstract
Underlying stromal cells are essential for the normal development of epithelial cells (EC) at mucosal surfaces. Recent studies from our laboratory have shown that uterine stromal cells regulate EC integrity, measured as transepithelial resistance (TER) as well as tumor necrosis factor alpha {alpha} (TNF{alpha}) secretion by EC in culture. Using stromal cells in co-culture with polarized EC grown on inserts, we found that stromal cells produce soluble mediators that increase TER and decrease TNF{alpha} secretion. The purpose of the present study was to identify the mechanism(s) whereby stromal cells exert their effects on uterine epithelium. We report that hepatocyte growth factor (HGF), a known mesenchymal growth factor that mediates EC proliferation, increases TER, while at the same time, decreases apical TNF{alpha} release. When EC and/or stromal cells were incubated with anti-HGF or anti-HGF receptor (HGFR) antibody prior to HGF, HGF effects were blocked. These findings indicate that EC express the receptor for HGF at their basolateral surfaces and that HGFR mediates the effects of HGF on TER and TNF{alpha}. Neutralization of stromal cell secretions with HGF- and HGFR-antibodies demonstrate that stromal-derived HGF is the mediator of epithelial cell TER. In contrast, neither anti-HGF antibody nor HGFR antibody had any effect on stromal cell induced decreases in TNF{alpha} secretion. From these results we conclude that stromal cell regulation of EC TER is mediated through the secretion of stromal HGF. Further, since neutralization of stromal media failed to affect TNF{alpha} secretion, these findings suggest that other growth factors, in addition to HGF, affect EC cytokine production.

Key words: Female Reproductive Tract • Immunology • Estradiol • Growth factors • Uterus


This article has been cited by other articles:


Home page
 J. Immunol.Home page
C. R. Wira, R. M. Rossoll, and R. C. Young
Polarized Uterine Epithelial Cells Preferentially Present Antigen at the Basolateral Surface: Role of Stromal Cells in Regulating Class II-Mediated Epithelial Cell Antigen Presentation
J. Immunol., August 1, 2005; 175(3): 1795 - 1804.
[Abstract] [Full Text] [PDF]


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