Interleukin-22 Promotes Wound Repair in Diabetes by Improving Keratinocyte Pro-Healing Functions

Simona Avitabile, Teresa Odorisio, Stefania Madonna, Stefanie Eyerich, Liliana Guerra, Kilian Eyerich, Giovanna Zambruno, Andrea Cavani, Francesca Cianfarani

Research output: Contribution to journalArticle

Abstract

Impaired re-epithelialization, imbalanced expression of cytokines and growth factors, and vascular disease contribute to healing impairment in diabetes. IL-22, a pro-inflammatory cytokine mediating a cross-talk between immune system and epithelial cells, has been shown to have a role in repair processes. In this study we aimed to investigate IL-22 regenerative potential in the poor healing context of diabetic wounds. By using streptozotocin-induced diabetic mice, we demonstrated that IL-22 wound treatment significantly accelerated the healing process, by promoting re-epithelialization, granulation tissue formation, and vascularization. Improved re-epithelialization was associated with increased keratinocyte proliferation and signal transducer and activator of transcription 3 (STAT3) activation. We showed that endogenous IL-22 content was reduced at both mRNA and protein level during the inflammatory phase of diabetic wounds, with fewer IL-22-positive cells infiltrating the granulation tissue. We demonstrated that IL-22 treatment promoted proliferation and injury repair of hyperglycemic keratinocytes and induced activation of STAT3 and extracellular signal-regulated kinase transduction pathways in keratinocytes grown in hyperglycemic condition or isolated from diabetic patients. Finally, we demonstrated that IL-22 treatment was able to inhibit diabetic keratinocyte differentiation while promoting vascular endothelial growth factor release. Our data indicate a pro-healing role of IL-22 in diabetic wounds, suggesting a therapeutic potential for this cytokine in diabetic ulcer management.

Original languageEnglish
Pages (from-to)2862-2870
Number of pages9
JournalJournal of Investigative Dermatology
Volume135
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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