IL-36γ inhibits differentiation and induces inflammation of keratinocyte via Wnt signaling pathway in psoriasis

Abstract

Psoriasis is a common inflammatory skin disease characterized by abnormal keratinocyte inflammation and differentiation that has a major impact on patients' quality of life. IL-36γ, a member of IL-36 cytokine family, is highly expressed in psoriasis and plays an important role in inflammation response and differentiation. However, the function of IL-36γ in differentiation and inflammation of keratinocyte in psoriasis has not been clearly identified. Thus, this study aimed to investigate the role of IL-36γ on differentiation and inflammation in HaCaT cells. HaCaT cells were divided into three groups: (1) Control group; (2) IL-36γ (100 ng/mL) group; (3) IL-36γ (100 ng/mL) + IWP-2 (1μM) group. Real time PCR was used to detect gene expression; the inflammation cytokines were examined by ELISA. We showed that treatment of HaCaT cells with IL-36γ significantly upregulated the expression levels of β-catenin, cyclin D1, and ki-67. IL-36γ also promoted the production of the inflammatory cytokines IFN-γ, IL-1β and IL-6, suppressed the expression of filaggrin, involucrin, keratin 1 and keratin 5. Meanwhile, we demonstrated the role of IWP-2, an inhibitor of the Wnt signaling pathway, in IL-36γ-treated HaCaT cells. Collectively, our findings suggest that IL-36γ inhibits differentiation and induces inflammation of keratinocyte via Wnt signaling pathway in psoriasis, this indicated that downregulation of IL-36γ may be a potential therapeutic option in psoriasis.

FGF19 sustains the high proliferative ability of keratinocytes in psoriasis through the regulation of Wnt/GSK‐3β/β‐catenin signalling via FGFR4

“…Similarly, the inhibition of β‐catenin restricts IL‐22‐induced keratinocyte proliferation by downregulating the expression of Wnt target genes . The treatment of HaCaT cells with IL‐36γ induces an increase in the expression levels of β‐catenin, cyclin D1, and Ki‐67, which may contribute to the hyperproliferation of keratinocytes in psoriasis . Therefore, the inhibition of Wnt/β‐catenin signalling may be a potential therapeutic option for psoriasis.…”

IL‐17A synergistically enhances TLR3‐mediated IL‐36γ production by keratinocytes: A potential role in injury‐amplified psoriatic inflammation

“…The role of IL‐36γ in psoriasis pathogenesis is increasingly recognized . Previous reports have shown that IL‐36γ induced proinflammatory mediators, as well as proliferation in keratinocytes . In this study, we hypothesized that dsRNA and IL‐17A–mediated innate immune response resulted in the acute exacerbation of inflammatory phenotype of keratinocytes, by synergistically enhancing expression of IL‐36γ.…”

“…[17][18][19] Previous reports have shown that IL-36γ induced proinflammatory mediators, as well as proliferation in keratinocytes. [13,20,21] In this study, we hypothesized that dsRNA and IL-17A-mediated innate immune response resulted in the acute exacerbation of inflammatory phenotype of keratinocytes, by synergistically enhancing expression of IL-36γ. The subsequent mechanistic study revealed a crucial role for the transcriptional co-factor IκBζ in dsRNA/IL-17A-provoked synergistic effects in keratinocytes.…”

Pathogenic role of exosomes and microRNAs in HPV‐mediated inflammation and cervical cancer: A review

“…Therefore, exosomes probably play an immunomodulatory role in the CC microenvironment. The pro‐inflammatory cytokine, IL‐36γ, has the ability to induce inflammation in keratinocytes via the Wingless/integrase 1 signaling pathway . Rana and colleagues demonstrated the presence of IL‐36γ inside exosomes derived from polyinosinic:polycytidylic acid (poly(I:C))‐treated keratinocytes.…”