The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis

J Invest Dermatol. 2004 Jul;123(1):124-31. doi: 10.1111/j.0022-202X.2004.22736.x.

Abstract

Interleukin-6 (IL-6) is involved in the growth and differentiation of numerous cell types. In the skin it is produced primarily by keratinocytes. The transcription factor STAT3 is activated by cytokines of the IL-6 family. In this study, we examined the involvement of IL-6, soluble IL-6-receptor, and STAT3 in epidermal barrier repair after injury to the stratum corneum by tape-stripping. After barrier disruption in wild-type mice we found an increased immunostaining of IL-6 and IL-6R on epidermal keratinocytes at 15 min to 5 h after treatment. The increase in IL-6 and IL-6R was confirmed by western blotting using epidermal homogenates and was partially prevented by occlusion immediately after barrier disruption. In IL-6-deficient mice, epidermal barrier repair was reduced at 3-24 h after treatment. Topical application of IL-6 or Hyper-IL-6, a complex of IL-6 linked to the soluble IL-6 receptor, enhanced epidermal barrier repair in wild-type mice. Application of the fusion protein gp130-FC, a specific inhibitor of the agonist IL-6/sIL-6 receptor complex, delayed barrier repair in wild, but not in IL-6-deficient mice. STAT3 tyrosine phosphorylation was induced after barrier disruption in wild-type, but markedly reduced in IL-6-deficient mice. Our results indicate that the IL-6 cytokine system, particularly transsignalling via the soluble IL-6R, is critically involved in barrier repair after skin injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / pharmacology
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism
  • Epidermal Cells
  • Epidermis / injuries
  • Epidermis / metabolism*
  • Homeostasis / physiology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Keratinocytes / metabolism*
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / pharmacology
  • Mice
  • Mice, Hairless
  • Mice, Mutant Strains
  • Permeability
  • Phosphorylation
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / metabolism
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism
  • Wound Healing / drug effects
  • Wound Healing / physiology

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • Il6st protein, mouse
  • Interleukin-6
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Cytokine Receptor gp130