Evaluation of the effects of IL-22 on the proliferation and differentiation of keratinocytes in vitro

Abstract

Psoriasis is one of the most common chronic inflammatory skin diseases, it is characterized by hyperproliferation of keratinocytes and infiltration of inflammatory cells. Several in vitro studies have reported that interleukin (IL)-22 is involved in excessive proliferation and abnormal differentiation of human keratinocytes. However, the association between IL-22 and CCAAT enhancer binding protein a (C/EBPa) in the pathogenesis of psoriasis remains unclear. Therefore, the present study aimed to investigate the association between IL-22 and C/EBPa, and the effects of IL-22 on the proliferation and differentiation of keratinocytes. Keratinocytes were treated with different concentrations of IL-22 (30, 60 and 90 ng/ml) and subsequently cells were collected at different time intervals. The expression levels of the key molecules of the mitogen-activated protein kinase (MAPK) signaling pathway were detected using western blot analysis. In addition, the effect of IL-22 on the proliferation rate of keratinocytes and the mRNA expression levels of C/EBPa were determined using a Cell Counting Kit-8 assay and reverse transcription-quantitative PCR, respectively. Furthermore, keratinocytes were transfected with C/EBPa small interfering (si)RNA or control using Lipofectamine® 2000. The results revealed that IL-22 significantly induced the proliferation of keratinocytes and the expression of phosphorylated (p)-JNK, p-ERK and p-p38 (P<0.05). Additionally, IL-22 significantly inhibited the differentiation of keratinocytes, and the mRNA and protein expression of C/EBPa (P<0.05). Furthermore, downregulation of C/EBPa increased the proliferation rate of keratinocytes and reduced the expression levels of cytokeratin 10 and involucrin. Therefore, these results suggested that the effect of IL-22 on the proliferation and differentiation of keratinocytes may be mediated via the regulation of the MAPK signaling pathway and the expression of C/EBPa.