Mechanical stretch exacerbates imiquimod-induced dermatitis associated with increased IL-1β and IL-6 production.

Psoriasis vulgaris is a chronic inflammatory skin disease which tends to affect the extensor surface of the body. IL-17A and IL-23 antagonists are currently the main and powerful therapeutic choices but the skin areas which are subject to stretching, namely knees, elbows and the lower back, are often reluctant to treatments. ; Hence, we hypothesize that stretching has a dominant effect on psoriasis development. First, we found that, in imiquimod-treated psoriasis-like mouse model, mechanical stretch promotes a significant increase in clinical severity, epidermal thickness, and inflammatory cell infiltration of psoriasis. Transcriptomics profiling revealed that Il6 and Il1b genes are significantly upregulated and play a major role in the activation and recruitment of neutrophils, macrophages, and T cells in stretching group. Upstream analysis further identifies NF-κB as a critical transcription factor to drive pro-inflammatory cytokine expression during stretch application. Immunofluorescence staining confirmed the increased expression of IL-1β and IL-6. In summary, our findings uncover that the mechanical biology contributes to psoriasis progression mainly through enhancing the production of IL-1β and IL-6. To comprehensively and systemically identify the main molecular signal pathways involved in stretch-enhanced skin inflammation, the transcriptomes of the IMQ-treated skin tissues with skin stretch (n=5) or without skin stretch (n=4), were profiled and compared (FS/IMQ+ vs. NS/IMQ+) by mRNA microarray.