Role of IL-17 and TGF-β in peritoneal adhesion formation after surgical trauma

Wound Repair Regen. 2014 Sep-Oct;22(5):631-9. doi: 10.1111/wrr.12203. Epub 2014 Aug 26.

Abstract

Peritoneal adhesions are fibrous tissues formed after surgery. Both cytokines and transforming growth factors (TGFs) are involved in this process. The objective of this study was to investigate the cross talk between these entities. Peritoneal drainage fluid after surgery from patients and rodent models was examined by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter. Data showed that the concentrations of interferon (IFN)-γ and interleukin (IL)-17 reached their peaks 6-12 hours after surgery, whereas TGF-β1 concentrations showed two postoperative peak time points at 2 and 72-96 hours. By neutralizing IFN-γ, IL-17 6-12 hours, and TGF-β1 72-96 hours after surgery, the degree of adhesion reduced significantly. However, neutralizing TGF-β1 2 hours after surgery did not affect adhesion formation. Furthermore, in vitro studies showed that compared with the fibroblasts that were directly stimulated with TGF-β1, the prestimulation of IL-17 promoted plasminogen activator inhibitor-1 production while inhibiting tissue-type plasminogen activator production. Moreover, additional stimulation with IFN-γ enhanced this effect. Together, these data indicate that IL-17 may promote adhesion formation by increasing the reaction of fibroblasts against TGF-β1. Blocking IL-17 might have a therapeutic potential in preventing adhesion formation after surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Colectomy / adverse effects
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Interferon-gamma / immunology*
  • Interleukin-17 / immunology*
  • Male
  • Mice
  • Middle Aged
  • NIH 3T3 Cells
  • Peritoneal Diseases / etiology
  • Peritoneal Diseases / immunology*
  • Serpin E2 / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • Tissue Adhesions / etiology
  • Tissue Adhesions / immunology
  • Tissue Plasminogen Activator / metabolism
  • Transforming Growth Factor beta1 / immunology*

Substances

  • Interleukin-17
  • Serpin E2
  • Serpine2 protein, mouse
  • Transforming Growth Factor beta1
  • Interferon-gamma
  • Tissue Plasminogen Activator