The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis.
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.
Wang
Xu-Ping
XP
Department of Dermatology, University of Kiel, Germany.
Schunck
Michael
M
Kallen
Karl-Josef
KJ
Neumann
Claudia
C
Trautwein
Christian
C
Rose-John
Stefan
S
Proksch
Ehrhardt
E
D000287:Administration, Topical; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000494:pharmacology; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D010539:Permeability; D010766:Phosphorylation; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130