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Down-Regulation of Interleukin-1 Receptor Type 1 Expression Causes the Dysregulated Expression of CXC Chemokines in Endometriotic Stromal Cells: A Possible Mechanism for the Altered Immunological Functions in Endometriosis

Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita 879-5593, Japan

Address all correspondence and requests for reprints to: Dr. Masakazu Nishida, Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan. E-mail: nishida{at}med.oita-u.ac.jp.

To evaluate the involvement of chemokines in the pathogenesis of endometriosis, we investigated the expression of CXC chemokines in cultured ovarian endometriotic cyst stromal cells (ECSC), endometrial stromal cells with endometriosis (ESCwE), and normal endometrial stromal cells (NESC). Using ELISA, TNF- significantly enhanced the production of IL-8, growth-related oncogene , and epithelial neutrophil-activating peptide-78 in all cases of ECSC (n = 10), ESCwE (n = 6), and, NESC (n = 10). IL-1ß did not affect the production of these chemokines in eight of 10 cases of ECSC. In contrast, IL-1ß significantly enhanced the expression of these chemokines in all cases of ESCwE (n = 6) and NESC (n = 10). Western blot analysis revealed down-regulation of expression of IL-1 receptor type 1 (IL-1-R1) in all cases of ECSC with low response to IL-1ß (n = 8). In contrast, significant IL-1-R1 expression was detected in all cases of NESC. Although IL-1-R1 expression was detected in all cases of ESCwE (n = 6), its expression in ESCwE tended to decrease compared with that in NESC. Moreover, phosphorylation of inhibitor B- was detected in all cases of ESCwE and NESC after stimulation with IL-1ß, but not in ECSC with low response to IL-1ß (n = 8). In contrast, significant IL-1-R2 expression was detected in all cases of ECSC, ESCwE, and NESC. The present findings suggest that the dysregulation of IL-1/IL-1-R system relates to immunological dysfunction in endometriosis. The alteration of the CXC chemokines expression may be important for elucidation of the pathogenesis of endometriosis.

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