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Therapeutically Targeting the Inflammasome Product in a Chimeric Model of Endometriosis-Related Surgical Adhesions

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Abstract

Development of adhesions commonly occurs in association with surgery for endometriosis. Even in the absence of surgery, women with endometriosis appear to be at an enhanced risk of developing adhesions. In the current study, we utilized a chimeric mouse model of experimental endometriosis in order to examine the role of inflammasome activation in the development of postsurgical adhesions. Mice were randomized to receive peritoneal injections of human endometrial tissue fragments or endometrial tissue conditioned media (CM) from women with or without endometriosis 16 hours after ovariectomy and placement of an estradiol-releasing silastic capsule. A subset of mice receiving CM was also treated with interleukin (IL) I receptor antagonist (IL-Ira). Our studies demonstrate that peritoneal injection of endometrial tissue fragments near the time of surgery resulted in extensive adhesive disease regardless of tissue origin. However, adhesion scores were significantly higher in mice receiving CM from tissues acquired from patients with endometriosis compared to control tissue CM (P =.0001). Cytokine bead array analysis of endometrial CM revealed enhanced expression of IL-Iβ from patients with endometriosis compared to controls (P <.01). Finally, the ability of human tissue CM to promote adhesive disease was dramatically reduced in mice cotreated with IL-Ira (P <.0001). Our data implicate enhanced expression of IL-Iβ in women with endometriosis as a potential causal factor in their increased susceptibility of developing postsurgical adhesions. Thus, targeting inflammasome activation may be an effective strategy for the prevention of surgical adhesions in patients with endometriosis.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Women’s Reproductive Health Research Center, Vanderbilt University Medical Center, 1161 21st Ave S, MCN B-1100, Nashville, TN, 37232, USA

    Meredith M. Stocks MEd, Marta A. Crispens MD, Tianbing Ding PhD, Shilpa Mokshagundam BS, BA, Kaylon L. Bruner-Tran PhD & Kevin G. Osteen PhD

  2. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Kevin G. Osteen PhD

  3. VA Tennessee Valley Healthcare System, Nashville, TN, USA

    Kevin G. Osteen PhD

Authors
  1. Meredith M. Stocks MEd
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  2. Marta A. Crispens MD
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  3. Tianbing Ding PhD
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  4. Shilpa Mokshagundam BS, BA
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  5. Kaylon L. Bruner-Tran PhD
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  6. Kevin G. Osteen PhD
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Correspondence to Kevin G. Osteen PhD.

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Stocks, M.M., Crispens, M.A., Ding, T. et al. Therapeutically Targeting the Inflammasome Product in a Chimeric Model of Endometriosis-Related Surgical Adhesions. Reprod. Sci. 24, 1121–1128 (2017). https://doi.org/10.1177/1933719117698584

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  • DOI: https://doi.org/10.1177/1933719117698584

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