Mechanisms of epithelial thickening due to IL-1 signalling blockade and TNF-α administration differ during wound repair and regeneration

Differentiation. 2018 Jan-Feb:99:10-20. doi: 10.1016/j.diff.2017.12.001. Epub 2017 Dec 12.

Abstract

IL-1 and TNF-α are always present during wound repair, but their pleiotropic and synergistic effects are incompletely understood. In this work, we evaluated the role of IL-1 in wound repair, and examined whether TNF-α administration impaired scarless wound repair. First, we characterised wound repair in outbred CD-1 mice according to age and sex in an ear punch wound model. Then, we examined the effects of Interleukin 1 receptor antagonist (IL-1ra) and TNF-α placement inside ear wounds by means of loaded Heparin beads in young and middle-aged male and female mice. Wounds in middle-aged females repaired with scarless characteristics, whereas those in young males showed fibrotic scarring. Rather than improving wound repair in young males, IL-1 signalling blockade increased epithelial thickness and IL-1β and TNF-α expression, and diminished epidermal apoptosis. TNF-α impaired wound repair in middle-aged females, which exhibited acanthosis and overexpression of IL-1, but no change in apoptosis. These findings suggest that this mechanism of epidermal thickening differs from that observed in IL1-ra-treated animals.

Keywords: Ear-punch; Epithelial thickening; IL-1ra; Scarless healing; TNFα.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cicatrix / drug therapy*
  • Disease Models, Animal
  • Interleukin 1 Receptor Antagonist Protein / drug effects*
  • Mice, Inbred C57BL
  • Regeneration / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Wound Healing / drug effects*

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Tumor Necrosis Factor-alpha