Endogenous TSG-6 modulates corneal inflammation following chemical injury

Ocul Surf. 2024 Apr:32:26-38. doi: 10.1016/j.jtos.2023.12.007. Epub 2023 Dec 25.

Abstract

Purpose: Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) is upregulated in various pathophysiological contexts, where it has a diverse repertoire of immunoregulatory functions. Herein, we investigated the expression and function of TSG-6 during corneal homeostasis and after injury.

Methods: Human corneas, eyeballs from BALB/c (TSG-6+/+), TSG-6+/- and TSG-6-/- mice, human immortalized corneal epithelial cells and murine corneal epithelial progenitor cells were prepared for immunostaining and real time PCR analysis of endogenous expression of TSG-6. Mice were subjected to unilateral corneal debridement or alkali burn (AB) injuries and wound healing assessed over time using fluorescein stain, in vivo confocal microscopy and histology.

Results: TSG-6 is endogenously expressed in the human and mouse cornea and established corneal epithelial cell lines and is upregulated after injury. A loss of TSG-6 has no structural and functional effect in the cornea during homeostasis. No differences were noted in the rate of corneal epithelial wound closure between BALB/c, TSG-6+/- and TSG-6-/- mice. TSG-6-/- mice presented decreased inflammatory response within the first 24 h of injury and accelerated corneal wound healing following AB when compared to control mice.

Conclusion: TSG-6 is endogenously expressed in the cornea and upregulated after injury where it propagates the inflammatory response following chemical injury.

Keywords: Chemical injury; Cornea; Corneal epithelium; Extracellular matrix; Hyaluronan; Inflammation; TSG-6; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burns, Chemical* / metabolism
  • Burns, Chemical* / pathology
  • Cell Adhesion Molecules* / genetics
  • Cell Adhesion Molecules* / metabolism
  • Cornea / metabolism
  • Cornea / pathology
  • Corneal Injuries / chemically induced
  • Corneal Injuries / genetics
  • Corneal Injuries / metabolism
  • Corneal Injuries / pathology
  • Disease Models, Animal
  • Epithelium, Corneal* / metabolism
  • Epithelium, Corneal* / pathology
  • Eye Burns* / chemically induced
  • Eye Burns* / genetics
  • Eye Burns* / metabolism
  • Eye Burns* / pathology
  • Humans
  • Keratitis / metabolism
  • Keratitis / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microscopy, Confocal
  • Real-Time Polymerase Chain Reaction
  • Wound Healing* / physiology

Substances

  • Cell Adhesion Molecules
  • TNFAIP6 protein, human
  • Tnfaip6 protein, mouse