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Toll-like receptor 4-mediated growth of endometriosis by human heat-shock protein 70

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Title: Toll-like receptor 4-mediated growth of endometriosis by human heat-shock protein 70
Authors: Khan, Khaleque Newaz / Kitajima, Michio / Imamura, Takehito / Hiraki, Koichi / Fujishita, Akira / Sekine, Ichiro / Ishimaru, T / Masuzaki, Hideaki
Issue Date: Oct-2008
Publisher: Oxford University Press
Citation: Human Reproduction, 23(10), pp.2210-2219; 2008
Abstract: BACKGROUND: We investigated the role of human heat-shock protein 70 (Hsp70) in Toll-like receptor 4 (TLR4)-mediated growth of endometriosis. METHODS: TLR4 expression was examined in macrophages (Mφ) isolated in primary culture from the peritoneal fluid of women with and without endometriosis. The production of a number of macromolecules by non-treated Mφ, Hsp70-treated Mφ and after treatment with anti-TLR4 antibody was examined by enzyme linked immunosorbent assay (ELISA). The single and combined effects of Hsp70 and lipopolysaccharide (LPS) on the growth of endometrial stromal cells were analyzed by 5-bromo-2-deoxyuridine (BrdU) incorporation study. Hsp70 levels in eutopic and ectopic endometria were measured by ELISA. RESULTS: TLR4 was detected in isolated Mφ at protein and gene level. Hsp70 (10 μg/ml) significantly stimulated the production of hepatocyte growth factor, vascular endothelial cell growth factor, interleukin-6 and tumor necrosis factor alpha by Mφ derived from women with endometriosis compared with Mφ derived from women with no endometriosis (P < 0.05 for each). This effect of Hsp70 was abrogated after pretreatment of Mφ with anti-TLR4 antibody. BrdU incorporation indicated that Hsp70 significantly enhanced the growth of endometrial stromal cells (∼50% increase) from women with endometriosis compared to non-treated cells. A synergistic effect on cell proliferation was observed between exogenous Hsp70 and LPS and this was significantly suppressed by pretreatment of cells with anti-TLR4 antibody (P < 0.05). Tissue levels of Hsp70 were significantly higher in the eutopic endometria (P < 0.05) and opaque red lesions (P < 0.01) derived from women with endometriosis than from other peritoneal lesions or from women with no endometriosis. CONCLUSIONS: A prominent stress reaction was observed in blood-filled opaque red peritoneal lesions. Human Hsp70 induces pelvic inflammation and may be involved in TLR4-mediated growth of endometrial cells derived from women with endometriosis.
Description: without figures and tables
Keywords: Cell growth / Endometriosis / Hsp70 / LPS / Macrophages / TLR4
URI: http://hdl.handle.net/10069/22227
ISSN: 02681161
DOI: 10.1093/humrep/den195
Rights: © The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. / This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Reproduction following peer review. The definitive publisher-authenticated version Human Reproduction, 23(10), pp.2210-2219; 2008 is available online at: http://humrep.oxfordjournals.org/cgi/content/abstract/23/10/2210 .
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22227

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