Increase in the Expression of Leukocyte Elastase Inhibitor During Wound Healing in Corneal Endothelial Cells

Cell Tissue Res. 2015 Dec;362(3):557-68. doi: 10.1007/s00441-015-2223-7. Epub 2015 Jun 18.

Abstract

Tissue injury triggers a complex network of cellular and molecular responses. Although cell migration and proliferation are the most conspicuous, several other responses, such as apoptosis and increased protease activity, are necessary for a proper restitution of the tissue. In this work, we study the leukocyte elastase inhibitor (LEI) expression during wound healing of bovine corneal endothelial monolayers in culture. LEI is a multifunctional protein with anti-protease and anti-apoptotic activity. When properly cleaved, it is transformed into L-DNase II, a pro-apoptotic enzyme and translocated to the nucleus. We found that early after injury LEI increases its protein and mRNA expressions, without nuclear translocation and returns to basal levels immediately after wound closure. This increase is blocked by N-acetylcysteine, suggesting that production of reactive oxygen species immediately after wounding is involved in the LEI increase. Another finding of this work is that there is an acidification of the cells at the wound border which, in contrast to other cell types, does not determine nuclear translocation of the protein. Taken together, the results of this work suggest that the function of LEI during wound healing is related to its activity as a protease inhibitor and/or to its anti-apoptotic activity.

Keywords: Epithelia; Healing modes; Leukocyte elastase inhibitor; Serpin-B1; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling
  • Cattle
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology*
  • Endothelium, Corneal / pathology*
  • Fluorescent Antibody Technique
  • Hydrogen-Ion Concentration
  • Intracellular Space / metabolism
  • Leukocyte Elastase / antagonists & inhibitors*
  • Leukocyte Elastase / metabolism
  • Reactive Oxygen Species / metabolism
  • Serpins / metabolism*
  • Sus scrofa
  • Wound Healing*

Substances

  • Reactive Oxygen Species
  • Serpins
  • Leukocyte Elastase