Scholarlink

<p>Postoperative adhesions (PA) remain an untreatable complication of abdominal surgery. In this study, we analyzed the role of interleukin-8 (IL-8) in the formation of PA using human cells in vitro and cynomolgus monkeys in vivo, as rodents lack the IL-8 gene. In an in vitro chemotaxis assay, recombinant IL-8 attracted more human neutrophils than its functional homologue, CXCL1, reflecting the dual engagement of CXCR1/2. In the human mesothelial cell line MeT-5A, IL-8 induced TNF-α secretion, which was abolished by the anti-IL-8 antibody AMY109. Conversely, TNF-α dose-dependently upregulated IL-8, supporting a reciprocal amplification loop. Although IL-8 did not directly alter the expression of fibrotic genes in neutrophils or mesothelial cells, TNF-α upregulated <i>TGFB1</i> mRNA in neutrophils, linking early IL-8/TNF-α signaling to profibrotic cascades. In monkey PA models, IL-8 in the injured abdominal wall was upregulated at 6&#xa0;h post-surgery. Prophylactic AMY109 (10&#xa0;mg/kg, i.v.) reduced the abdominal-wall adhesion score (<i>P</i> &lt; 0.05) and tended to lower uterine adhesions (<i>P</i> = 0.0907). These findings suggest that IL-8 orchestrates neutrophil recruitment and crosstalk between neutrophils and mesothelial cells, amplifying inflammation and fibrosis, and that IL-8 blockade effectively attenuates PA formation. Targeting IL-8 therefore represents a promising pharmacological strategy to prevent PA.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

IL-8 contributes to postoperative adhesion formation through the crosstalk of neutrophils and mesothelial cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月19日

查看全文
  • Kenji Nakagawa,
  • Hiromi Tanimura,
  • Masaki Yamazaki,
  • Izumi Sato,
  • Shinta Kobayashi,
  • Miho Kohara,
  • Yuichiro Sakamoto,
  • Narumi Sakaguchi,
  • Atsuhiko Kato,
  • Masahiro Azuma,
  • Ayako Nishimoto-Kakiuchi,
  • Takehisa Kitazawa,
  • Ryo Konno,
  • Tadashi Sankai

摘要

Postoperative adhesions (PA) remain an untreatable complication of abdominal surgery. In this study, we analyzed the role of interleukin-8 (IL-8) in the formation of PA using human cells in vitro and cynomolgus monkeys in vivo, as rodents lack the IL-8 gene. In an in vitro chemotaxis assay, recombinant IL-8 attracted more human neutrophils than its functional homologue, CXCL1, reflecting the dual engagement of CXCR1/2. In the human mesothelial cell line MeT-5A, IL-8 induced TNF-α secretion, which was abolished by the anti-IL-8 antibody AMY109. Conversely, TNF-α dose-dependently upregulated IL-8, supporting a reciprocal amplification loop. Although IL-8 did not directly alter the expression of fibrotic genes in neutrophils or mesothelial cells, TNF-α upregulated TGFB1 mRNA in neutrophils, linking early IL-8/TNF-α signaling to profibrotic cascades. In monkey PA models, IL-8 in the injured abdominal wall was upregulated at 6 h post-surgery. Prophylactic AMY109 (10 mg/kg, i.v.) reduced the abdominal-wall adhesion score (P < 0.05) and tended to lower uterine adhesions (P = 0.0907). These findings suggest that IL-8 orchestrates neutrophil recruitment and crosstalk between neutrophils and mesothelial cells, amplifying inflammation and fibrosis, and that IL-8 blockade effectively attenuates PA formation. Targeting IL-8 therefore represents a promising pharmacological strategy to prevent PA.