Jones A M, Griffiths J L, Sanders A J, Owen S, Ruge F, Harding K G, Jiang W G
Cardiff China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Department of Wound Healing, Cardiff University School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Int J Mol Med. 2016 Sep;38(3):679-86. doi: 10.3892/ijmm.2016.2687. Epub 2016 Jul 21.
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.
慢性伤口给医疗服务带来了巨大负担,并与患者的发病率相关。因此需要新的方法来诊断和/或治疗有问题的伤口。白细胞介素(IL)-15是一种细胞因子,参与许多生物学过程和疾病状态,如炎症、愈合和癌症进展。本研究探讨了IL-15和IL-15受体α(IL-15Rα)在慢性伤口中的表达谱及其对角质形成细胞的影响。使用qPCR和免疫组织化学分析检测了愈合和未愈合慢性伤口中IL-15和IL-15Rα的表达。进一步研究了重组IL-15(rhIL-15)对人成人低钙温度(HaCaT)角质形成细胞生长和迁移潜能的影响。与未愈合的慢性伤口相比,愈合的慢性伤口中IL-15转录本表达略有升高,但无统计学意义。两种慢性伤口亚型中IL-15蛋白染色均极少。相比之下,与愈合的慢性伤口相比,未愈合的慢性伤口中IL-15Rα转录本和蛋白表达均增强。用rhIL-15处理HaCaT细胞通常会促进细胞生长并促进迁移。小分子抑制剂分析表明,rhIL-15的促迁移作用可能与ERK、AKT、PLCγ和FAK信号通路有关。IL-15可能促进角质形成细胞的愈合特性,并且在慢性伤口中观察到IL-15Rα的差异表达。总之,这可能意味着这种白细胞介素在伤口愈合中起复杂作用。