title: The clinical significance and impact of interleukin 15 on keratinocyte cell growth and migration.
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.
authors.affiliation: Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Jones
authors.affiliation: Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Griffiths
authors.affiliation: Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Sanders
authors.affiliation: Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: S
authors.initials: S
authors.lastname: Owen
authors.affiliation: Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: F
authors.initials: F
authors.lastname: Ruge
authors.affiliation: Department of Wound Healing, Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: K G
authors.initials: KG
authors.lastname: Harding
authors.affiliation: Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: W G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002908:Chronic Disease; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics; D014947:Wounds and Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D011994:Recombinant Proteins