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Mechanical Stretch Stimulates Interleukin-8 Production in Endometrial Stromal Cells: Possible Implications in Endometrium-Related Events

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan

Address all correspondence and requests for reprints to: Dr. Yutaka Osuga, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: yutakaos-tky{at}umin.ac.jp.

Uterine movement is suggested to play roles in various events related to the uterus. In view of the current concept underscoring the biological implications of mechanical stretch, we speculated that the mechanical stretch exerted by uterine movement might stimulate the production of biochemical mediators in endometrial cells and contribute to inflammation-associating processes, such as menstruation and endometriosis. To address the possible effects of mechanical stretch in the endometrium, endometrial stromal cells (ESC) were cultured on flexible-bottomed culture plates, and cyclic stretch (25% elongation) was applied in serum-free conditions at a rate of two cycles per minute using a computer-operated cell tension system. IL-8 concentrations in the conditioned medium were measured using ELISA, and IL-8 mRNA expression in ESC was measured by RT-PCR. Cyclic stretch increased the secretion of IL-8 from ESC. The increase in IL-8 secretion was inhibited by PD98059, an inhibitor of extracellular signal-regulated kinase 1/2. The increase was also inhibited by progesterone. In addition, the conditioned medium of ESC cultured with cyclic stretch stimulated the mRNA expression of IL-8 in ESC cultured under stationary conditions. These findings imply that uterine movement has an impact on endometrium-related physiology and pathology by stimulating the production of a biochemical mediator(s) in the endometrium.

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