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Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Interleukin-8 Induces Proliferation of Endometrial Stromal Cells: a Potential Autocrine Growth Factor*
Endometriosis, a common disease among women of reproductive age, is characterized by the presence of endometrial-like tissue outside the uterus. We and others showed that several cytokine levels, including interleukin-8 (IL-8) and tumor necrosis factor-α (TNFα), are elevated in the peritoneal fluid of women with endometriosis compared with those in women without endometriosis. We also demonstrated that the addition of IL-8 to the culture medium stimulated the proliferation of cultured endometriotic stromal cells. TNFα is a multipotent cytokine that induces IL-8 production in various cell types. Therefore, we hypothesized that TNFα may also contribute to the pathogenesis of endometriosis by inducing the production of IL-8. To test this hypothesis, we analyzed the peritoneal fluid concentrations of IL-8 and TNFα using enzyme-linked immunosorbent assay (ELISA). We observed a significant correlation between the levels of TNFα and IL-8 in the peritoneal fluid of endometriosis patients. We also obtained the endometriotic stromal cells from chocolate cyst linings of the ovary. The expression of the receptors for TNFα (TNFR) was examined by RT-PCR. We observed the expression of both TNFR-I and TNFR-II genes in endometriotic stromal cells. The expression of IL-8 gene and protein was analyzed by Northern blot hybridization and enzyme-linked immunosorbent assay, respectively. TNFα induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNFα promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNFα were abolished by adding anti-IL-8 antibody. We demonstrated for the first time that TNFα stimulated proliferation of endometriotic stromal cells through induction of IL-8 gene and protein expression. We concluded that the TNFα may be one of the essential factors for the pathogenesis of endometriosis.
The Journal of Clinical Endocrinology & Metabolism – Oxford University Press
Published: Feb 1, 2000
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