Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation

Cell Death Dis. 2018 Dec 5;9(12):1181. doi: 10.1038/s41419-018-1226-1.

Abstract

Mechanical damage on the skin not only affects barrier function but also induces various immune responses, which trigger or exacerbate skin inflammation. However, how mechanical damage-induced skin inflammation is regulated remains incompletely understood. Here, we show that keratinocytes express the long-chain fatty-acid elongase Elovl6. Mice deficient in Elovl6 showed higher levels of cis-vaccenic acid (CVA) in the epidermis and severe skin inflammation induced by mechanical damage due to tape stripping than did wild-type mice. CVA accelerated tape stripping-triggered keratinocyte death and release of danger-associated molecular patterns (DAMPs) such as high-mobility group box 1 protein (HMGB-1) and IL-1α, which induced production of proinflammatory cytokines and chemokines IL-1β and CXCL-1 by keratinocytes. Our results demonstrate that Elovl6 regulates mechanical damage-triggered keratinocyte death and the subsequent dermatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / deficiency
  • Acetyltransferases / genetics*
  • Animals
  • Biomechanical Phenomena
  • Cell Death / genetics
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / metabolism
  • Dermatitis / genetics*
  • Dermatitis / metabolism
  • Dermatitis / pathology
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Fatty Acid Elongases
  • Gene Expression Regulation
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Mechanotransduction, Cellular*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oleic Acids / metabolism

Substances

  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Elovl6 protein, mouse
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • IL1B protein, mouse
  • Interleukin-1alpha
  • Interleukin-1beta
  • Oleic Acids
  • cis-vaccenic acid
  • Acetyltransferases
  • Fatty Acid Elongases