Stocks Meredith M, Crispens Marta A, Ding Tianbing, Mokshagundam Shilpa, Bruner-Tran Kaylon L, Osteen Kevin G
1 Department of Obstetrics and Gynecology, Women's Reproductive Health Research Center, Vanderbilt University Medical Center, Nashville, TN, USA.
2 Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Reprod Sci. 2017 Aug;24(8):1121-1128. doi: 10.1177/1933719117698584. Epub 2017 Mar 21.
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) 1 receptor antagonist (IL-1ra). 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-1β 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-1ra ( P < .0001). Our data implicate enhanced expression of IL-1β 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.
粘连的形成通常与子宫内膜异位症手术相关。即使没有手术，患有子宫内膜异位症的女性似乎发生粘连的风险也会增加。在本研究中，我们利用实验性子宫内膜异位症的嵌合小鼠模型，以研究炎性小体激活在术后粘连形成中的作用。在卵巢切除和植入释放雌二醇的硅橡胶胶囊16小时后，将小鼠随机分为接受腹腔注射来自患有或未患有子宫内膜异位症女性的人子宫内膜组织碎片或子宫内膜组织条件培养基（CM）。接受CM的一部分小鼠也用白细胞介素（IL）-1受体拮抗剂（IL-1ra）进行治疗。我们的研究表明，手术时附近腹腔注射子宫内膜组织碎片会导致广泛的粘连疾病，而与组织来源无关。然而，与对照组织CM相比，接受来自子宫内膜异位症患者组织的CM的小鼠粘连评分显著更高（P = .0001）。对子宫内膜CM的细胞因子珠阵列分析显示，与对照组相比，子宫内膜异位症患者IL-1β的表达增强（P < .01）。最后，在与IL-1ra共同处理的小鼠中，人组织CM促进粘连疾病的能力显著降低（P < .0001）。我们的数据表明，子宫内膜异位症女性中IL-1β表达增强是其术后粘连易感性增加的潜在因果因素。因此，靶向炎性小体激活可能是预防子宫内膜异位症患者手术粘连的有效策略。
