@article{oai:nagasaki-u.repo.nii.ac.jp:00018268,
 author = {Khan, Khaleque Newaz and Kitajima, Michio and Imamura, Takehito and Hiraki, Koichi and Fujishita, Akira and Sekine, Ichiro and Ishimaru, T and Masuzaki, Hideaki},
 issue = {10},
 journal = {Human Reproduction},
 month = {Oct},
 note = {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., without figures and tables, Human Reproduction, 23(10), pp.2210-2219; 2008},
 pages = {2210--2219},
 title = {Toll-like receptor 4-mediated growth of endometriosis by human heat-shock protein 70},
 volume = {23},
 year = {2008}
}