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Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation.
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-26 , DOI: 10.1038/s41598-019-54175-1 Naoki Uyama 1 , Hiroko Tsutsui 1 , Songtao Wu 1 , Koubun Yasuda 2 , Etsuro Hatano 1 , Xian-Yang Qin 3 , Soichi Kojima 3 , Jiro Fujimoto 1
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-26 , DOI: 10.1038/s41598-019-54175-1 Naoki Uyama 1 , Hiroko Tsutsui 1 , Songtao Wu 1 , Koubun Yasuda 2 , Etsuro Hatano 1 , Xian-Yang Qin 3 , Soichi Kojima 3 , Jiro Fujimoto 1
Affiliation
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Postoperative adhesion formation often ruins the quality of life or is an obstacle to illnesses with curative operation such as cancer. Previously we demonstrated that interferon-γ-promoted fibrin deposition drove postoperative adhesion formation. However, its underlying cellular and molecular mechanisms remain poorly understood. We found that myofibroblasts of the adhesion predominantly expressed signature molecules of mesothelial cells that line the serosa. Microarray analysis revealed IL-6 as a key underlying player, supported by elevated IL-6 levels in the peritoneal fluid of post-laparotomy human subjects. Injured serosa of cecum-cauterized mice also exhibited induction of Il6, which was followed by Tnf, concomitant with rapid accumulation of neutrophils, substantial population of which expressed TGF-β1, a master regulator of fibrosis. Besides, neutrophil-ablated mice showed reduction in induction of the adhesion, suggesting that TGF-β1+neutrophils triggered the adhesion. Human neutrophils expressed TGFB1 in response to TNF-α and TNF in response to IL-6. Moreover, anti-IL-6 receptor monoclonal antibody abrogated neutrophil recruitment and adhesion formation. Thus, IL-6 signaling represents a potential target for the prevention of postoperative adhesions.
中文翻译：
抗白介素6受体抗体治疗可改善术后粘连形成。
术后粘连形成通常会破坏生活质量，或成为治愈性疾病（例如癌症）的障碍。以前我们证明干扰素-γ促进纤维蛋白沉积驱动术后粘连形成。然而，其潜在的细胞和分子机制仍知之甚少。我们发现，粘附的成肌纤维细胞主要表达衬在浆膜上的间皮细胞的标志性分子。微阵列分析显示，IL-6是关键的潜在参与者，并受到开腹手术后人类受试者腹膜液中IL-6水平升高的支持。盲肠灼伤小鼠的浆膜也表现出诱导的Il6，其后是Tnf，伴随着中性粒细胞的快速积累，其中大量的中性粒细胞表达了TGF-β1，它是纤维化的主要调控因子。此外，嗜中性粒细胞消融的小鼠显示出减少的粘附诱导，表明TGF-β1+嗜中性粒细胞触发了粘附。人中性粒细胞表达TGFB1响应TNF-α和TNF响应IL-6。而且，抗IL-6受体单克隆抗体消除了中性粒细胞的募集和粘附形成。因此，IL-6信号传导代表了预防术后粘连的潜在目标。
更新日期：2019-11-27
中文翻译：
抗白介素6受体抗体治疗可改善术后粘连形成。
术后粘连形成通常会破坏生活质量，或成为治愈性疾病（例如癌症）的障碍。以前我们证明干扰素-γ促进纤维蛋白沉积驱动术后粘连形成。然而，其潜在的细胞和分子机制仍知之甚少。我们发现，粘附的成肌纤维细胞主要表达衬在浆膜上的间皮细胞的标志性分子。微阵列分析显示，IL-6是关键的潜在参与者，并受到开腹手术后人类受试者腹膜液中IL-6水平升高的支持。盲肠灼伤小鼠的浆膜也表现出诱导的Il6，其后是Tnf，伴随着中性粒细胞的快速积累，其中大量的中性粒细胞表达了TGF-β1，它是纤维化的主要调控因子。此外，嗜中性粒细胞消融的小鼠显示出减少的粘附诱导，表明TGF-β1+嗜中性粒细胞触发了粘附。人中性粒细胞表达TGFB1响应TNF-α和TNF响应IL-6。而且，抗IL-6受体单克隆抗体消除了中性粒细胞的募集和粘附形成。因此，IL-6信号传导代表了预防术后粘连的潜在目标。
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