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Interleukin-6- and tumour necrosis factor α-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis


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Title: Interleukin-6- and tumour necrosis factor α-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis
Authors: Khan, Khaleque Newaz / Masuzaki, Hideaki / Fujishita, Akira / Kitajima, Michio / Hiraki, Koichi / Sekine, Ichiro / Matsuyama, Toshifumi / Ishimaru, Tadayuki
Issue Date: Oct-2005
Publisher: Oxford University Press
Citation: Human Reproduction, 20(10), pp.2715-2723; 2005
Abstract: Background: We investigated the expression of the hepatocyte growth factor (HGF) gene and protein by the stromal cells derived from women with or without endometriosis and its regulation by interleukin-6 (IL-6) and tumour necrosis factor α (TNFα). Methods: Stromal cells immunoreactive to vimentin were isolated from the eutopic and ectopic endometrium of 18 infertile women with endometriosis and 12 women without endometriosis. The production of HGF in the culture media of basal and IL-6- or TNFα-stimulated stromal cells was examined with an enzyme-linked immunosorbent assay. The mRNA expression of HGF and its receptor c-Met in the stroma was investigated by RT-PCR. The localization of HGF and c-Met in isolated stromal cells and in intact tissue was examined by immunohistochemistry. The effect of HGF on the growth of stromal cells alone or in combination with IL-6 or TNFα was examined in a bromodeoxyuridine (BrdU) incorporation study. Results: The production of HGF in the culture medium of stromal cells was significantly increased after single or combined treatment with either IL-6 or TNFα when compared with non-treated cells. The production of HGF by stromal cells derived from the eutopic endometrium of women with endometriosis was significantly higher than that of cells from women without endometriosis. This effect was paralleled by increased expression of HGF and c-Met mRNA, as demonstrated by RT-PCR. The BrdU incorporation study indicated that the addition of HGF enhanced the growth of endometrial and endometriotic stroma alone or in combination with IL-6 or TNFα. Conclusion: IL-6 and TNFα are involved in the production of HGF by endometrial stromal cells and may be involved in the growth of endometriosis by an autocrine mechanism.
Keywords: Cell growth / Endometriosis / Hepatocyte growth factor / IL-6 / TNFα
URI: http://hdl.handle.net/10069/34524
ISSN: 02681161
DOI: 10.1093/humrep/dei156
Rights: © The Author 2005. 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, 20(10), pp.2715-2723; 2005 is available online at: http://dx.doi.org/10.1093/humrep/dei156
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34524

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