{"paper_id":"1a45533a-a576-4ed7-a433-aa6cd831c23b","body_text":"Abstract\nPurpose\nThe production of epithelial neutrophil activating peptide-78 (NA-78) and the interleukins IL-8 and IL-6 by endometrial stromal cells is stimulated by pro-inflammatory interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). IL-8 is suggested to play a role in the pathogenesis of endometriosis, and in these women the peritoneal fluid concentrations of ENA-78 and IL-8 are increased. TNF-α has been tested together with interferon-γ because of their cooperative stimulation of IL-6. The release of IL-8, however, is inhibited with increasing interferon levels. The aim of the study was the analysis of the production of ENA-78, IL-6 and IL-8 by cultured human endometrial stromal cells in the presence of varying concentrations of IL-1β, TNF-α, and interferon-γ.\nMethods\nEutopic endometrial tissue was obtained from seven cycling, endometriosis-free women undergoing laparoscopy for reasons of infertility or pain. The release of ENA-78, IL-8 and IL-6 by the isolated and monolayer cultured stromal cell fraction in the presence of IL-1β (0.08 to 50 ng/mL), TNF-α, and interferon-γ (both 20 to 500 ng/mL) was determined.\nResults\nIL-1β stimulated the production of IL-8, IL-6, and ENA-78 dose dependently from 0.08 to 2.0 ng/mL (ENA-78) or to 10 ng/mL (IL-8, IL-6); at 50 ng/mL a decrease in release was observed for IL-8 and IL-6. TNF-α stimulation yielded a plateau between 20 and 100 ng/mL. Interferon-γ stimulated IL-6 and inhibited IL-8 production above 20 ng/mL. ENA-78 release was largely unaffected by interferon-γ.\nConclusions\nIL-1β and TNF-α stimulate stromal cytokine production cumulatively with different dose–response curves. The presence of interferon-γ has opposite effects on IL-8 and IL-6. TNF-α and interferon-γ should be investigated separately in future in vitro studies with endometrial cells and explants.\nSimilar content being viewed by others\nReferences\nKoch AE, Volin MV, Woods JM et al (2001) Regulation of angiogenesis by the C-X-C chemokines interleukin-8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. Arthritis Rheumatol 44:31–40\nWalz A, Schmutz P, Mueller C, Schnyder S (1997) Regulation and function of CXC chemokine ENA-78 in monocytes and its role in disease. J Leukoc Biol 62:604–611\nNasu K, Arima K, Kai K, Fujisawa K, Nishida M, Miyakawa I (2001) Expression of epithelial neutrophil-activating peptide 78 in cultured human endometrial stromal cells. 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Hum Reprod 22:427–433\nConflict of interest statement\nNone.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nBersinger, N.A., Günthert, A.R., McKinnon, B. et al. Dose–response effect of interleukin (IL)-1β, tumour necrosis factor (TNF)-α, and interferon-γ on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells. Arch Gynecol Obstet 283, 1291–1296 (2011). https://doi.org/10.1007/s00404-010-1520-3\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-010-1520-3","source_license":"CC0","license_restricted":false}