Interleukin-6- and tumour necrosis factor α-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis
Source: Human Reproduction, Volume 20, Number 10, October 2005 , pp. 2715-2723(9)
Publisher: Oxford University Press
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.
Document Type: Research Article
Affiliations: 1: Department of Obstetrics and Gynecology, 2: Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University, 3: Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Publication date: 2005-10-01
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.