Regulation of Hepatocyte Growth Factor by Basal and Stimulated Macrophages in Women with Endometriosis. Human Reprod

BACKGROUND: The different macromolecules as secreted by macrophages (Mw) in the pelvic environment are believed to enhance the growth of endometriosis. However, the possible mediator that stimulates Mw for the production of different growth factors is not well described. Therefore, we investigated the possible production of hepatocyte growth factor (HGF) by the basal and lipopolysaccharide (LPS)-stimulated Mw derived from women with or without endometriosis. METHODS: Using primary culture and 4-well chamber slides, adherent Mw immunoreactive to CD68 were isolated from the peritoneal fluid (PF) of 20 infertile women with endometriosis and 12 women without endometriosis. The proliferation of basal and LPS-treated Mw was investigated by the dimethylthiazole tetrazolioum bromide (MTT) assay. The production of HGF in the culture media of basal and LPS-stimulated Mw was examined by enyme-linked immunosorbent assay. The expression of mRNA for HGF and its receptor, c-Met, in the Mw was investigated by RT–PCR. The effect of HGF on the growth of endometrial cells and Mw was analysed by bromodeoxyuridine (BrdU) incorporation. RESULTS: A>100 % increase in the prolifer-ation of peritoneal Mw derived from women with endometriosis, and particularly of those harbouring dominant red lesions, was observed after treatment with LPS (P < 0.05). A 4- and 3-fold increase in the production of HGF was observed by the LPS-treated Mw derived from women with stage I–II endometriosis and stage III–IV endo-metriosis, respectively, when compared with non-LPS-treated Mw (P < 0.001). At the transcriptional level, we