IL-33 contributes to disease severity in Psoriasis-like models of mouse.

Immune cells infiltrating the psoriatic skin secrete high amounts of pro-inflammatory cytokines IL-17, TNF-α, IL-21 and IL-36 resulting in chronic inflammation. However, the exact cellular and molecular mechanisms have not been fully understood. We report here elevation of IL-33 expression in psoriatic lesions. Studies in imiquimod (IMQ)-induced mice with psoriatic inflammation confirmed a critical role for IL-33 in driving the disease. IL-33 reduces the CD4+ and CD8+ cells, inhibits autophagy in IMQ-treated mouse skin, and promoted tyrosyl phosphorylation of STAT3. Thus, IL-33 appears to be a major risk factor for severity of psoriasis-like skin inflammation. Our findings may open new perspectives for understanding the mechanisms and developing a therapeutic strategy for psoriasis.

LncRNA MALAT-1 regulates the growth of interleukin-22-stimulated keratinocytes via the miR-330-5p/S100A7 axis.

Psoriasis is a chronic autoimmune disorder related to abnormal keratinocyte proliferation. Long noncoding RNAs (lncRNAs) are significant regulators in the progression of skin diseases. In this study, we explored how lncRNA MALAT-1 controls the pathogenesis of psoriasis by examining its impact on keratinocyte proliferation, inflammation, and apoptosis. A psoriasis cell model was established by treating HaCaT keratinocytes with the inflammatory factor, IL-22 (100 ng/ml), for 24 h. The MALAT-1 and S100A7 levels in psoriatic lesions, normal skin tissues, and IL-22-stimulated HaCaT cells were determined by RT-qPCR and western blotting. Cell proliferation, inflammation, and apoptosis were detected by the MTT assay, western blotting, and flow cytometry analysis, respectively. Bioinformatics analysis was used to identify the miRNAs that bind to MALAT-1 and S100A7. The relationships between MALAT-1 or miR-330-5p and S100A7 were assessed using a luciferase reporter assay. The MALAT-1 and S100A7 levels were upregulated in both psoriatic lesion samples and IL-22-stimulated HaCaT cells. Silencing MALAT-1 significantly reversed the IL-22-stimulated promotion of HaCaT proliferation and changes in Ki67 and KRT5/14/1/10 protein levels, and MALAT-1 deficiency also reversed the upregulation of TNF-α, IL-17, and IL-23 protein levels as well as suppression of cell apoptosis. As a ceRNA, MALAT-1 competed with S100A7 to prevent miR-330-5p-induced inhibition of S100A7 expression. There was a negative correlation between miR-330-5p and MALAT-1 (or S100A7) expression in psoriatic lesion tissues. In response to IL-22 treatment, miR-330-5p silencing eliminated the effects of MALAT-1 knockdown in HaCaT cells. Thus, these findings demonstrated that MALAT-1 modulates the IL-22-induced changes in HaCaT cells through the miR-330-5p/S100A7 axis.