NB-UVB irradiation downregulates keratin-17 expression in keratinocytes by inhibiting the ERK1/2 and STAT3 signaling pathways.

Abstract

Keratin-17 (K17) is a cytoskeletal protein produced by keratinocytes (KCs), which is overexpressed in psoriasis and may play a pivotal role in its pathogenesis. Narrow-band ultraviolet B (NB-UVB) irradiation is used as a general treatment for psoriasis, although its impact on K17 expression has yet to be determined. In this study, we aimed to investigate the effect of NB-UVB irradiation on K17 expression and its signaling pathways. After exposure to NB-UVB irradiation, immortalized human keratinocytes (HaCaT cells) were analyzed by flow cytometry, CCK-8 assays and transmission electron microscopy to examine proliferation. Meanwhile, K17 expression in primary human epithelial keratinocytes was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis and immunofluorescence. HaCaT cells pre-incubated with PD-98059 and piceatannol were subjected to western blot analysis to examine ERK1/2 and STAT3 phosphorylation. The ears of mice treated with imiquimod (IMQ) and irradiated by NB-UVB were taken to examine K17 expression by qRT-PCR, western blot analysis, and immunofluorescence. Our results showed that 400mJ/cm2 of NB-UVB irradiation was the maximum tolerable dose for HaCaT cells and could cause inhibited HaCaT cell proliferation and moderate increase of the early apoptosis. Furthermore, NB-UVB irradiation could downregulate K17 expression by inhibiting the ERK1/2 and STAT3 signaling pathways. In experiments conducted in vivo, NB-UVB irradiation with doses of MED or higher could eliminate the IMQ-induced psoriasis-like dermatitis and inhibit K17 expression. These results indicated that NB-UVB irradiation may eliminate chronic psoriatic plaques by suppressing K17 expression via the ERK1/2 and STAT3 signaling pathways.