Tumor necrosis factor-alpha promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression

Endometriosis, a common disease among women of reproductive age, is charact erized by the presence of endometrial-like tissue out side the uterus. me a nd others showed that several cytokine levels, including interleukin-8 (IL- 8) and tumor necrosis factor-alpha (TNF alpha), are elevated in the periton eal fluid of women with endometriosis compared with those in women without endometriosis. me also demonstrated that the addition of IL-8 to the cultur e medium stimulated the proliferation of cultured endometriotic stromal cel ls. TNF alpha is a multipotent cytokine that induces IL-8 production in var ious cell types. Therefore, we hypothesized that TNF alpha may also contrib ute 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 TNF alpha using enzyme-linked immunosorbent assay (ELISA). me o bserved a significant correlation between the levels of TNF alpha and IL-8 in the peritoneal fluid of endometriosis patients, We also obtained the end ometriotic stromal cells from chocolate cyst linings of the ovary. The expr ession of the receptors for TNF alpha (TNFR) was examined by RT-PCR. We obs erved the expression of both TNFR-I and TNFR-II genes in endometriotic stro mal cells. The expression of IL-8 gene and protein was analyzed by Northern blot hybridization and enzyme-linked immunosorbent assay, respectively TNF a induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNF alpha promoted the p roliferation of the endometriotic stromal cells, and the stimulatory effect s of TNF alpha were abolished by adding anti-IL-8 antibody. We demonstrated for the first time that TNF alpha stimulated proliferation of endometrioti c stromal cells through induction of IL-8 gene and protein expression. We c oncluded that the TNF alpha: may be one of the essential factors for the pa thogenesis of endometriosis.