The clinical significance and impact of interleukin 15 on keratinocyte cell growth and migration

Int J Mol Med. 2016 Sep;38(3):679-86. doi: 10.3892/ijmm.2016.2687. Epub 2016 Jul 21.

Abstract

Chronic wounds represent a significant burden to health services and are associated with patient morbidity. Novel methods to diagnose and/or treat problematic wounds are needed. Interleukin (IL)-15 is a cytokine involved in a number of biological processes and disease states such as inflammation, healing and cancer progression. The current study explores the expression profile of IL-15 and IL-15 receptor α (IL-15Rα) in chronic wounds and its impact on keratinocytes. IL-15 and IL-15Rα expression were examined in healing and non-healing chronic wounds using qPCR and immunohistochemical analysis. The impact of recombinant IL-15 (rhIL-15) on human adult low calcium temperature (HaCaT) keratinocyte growth and migratory potential was further examined. IL-15 transcript expression was slightly, though non-significantly elevated in healing chronic wounds compared with non-healing chronic wounds. IL-15 protein staining was minimal in both subtypes of chronic wounds. By contrast, IL-15Rα transcript and protein expression were both observed to be enhanced in non-healing chronic wounds compared with healing chronic wounds. The treatment of HaCaT cells with rhIL-15 generally enhanced cell growth and promoted migration. Analysis with small molecule inhibitors suggested that the pro-migratory effect of rhIL-15 may be associated with ERK, AKT, PLCγ and FAK signalling. IL-15 may promote healing traits in keratinocytes and the differential expression of IL-15Rα is observed in chronic wounds. Together, this may imply a complex role for this interleukin in wound healing.

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Chronic Disease
  • Gene Expression Profiling / methods
  • Humans
  • Immunohistochemistry
  • Interleukin-15 / genetics*
  • Interleukin-15 / metabolism
  • Interleukin-15 / pharmacology
  • Interleukin-15 Receptor alpha Subunit / genetics
  • Interleukin-15 Receptor alpha Subunit / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Wound Healing / drug effects
  • Wound Healing / genetics
  • Wounds and Injuries / genetics
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit
  • Recombinant Proteins