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Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale
Published on: May 28, 2021
CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
Yue Sun1,2, Jie Zhang2, Tianhang Zhai2
1Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
CCN1, an extracellular protein also known as cysteine-rich protein 61 (Cyr61), is a novel pro-inflammatory factor involved in the pathogenesis of rheumatoid arthritis. As an inflammatory disease, psoriasis is characterized by keratinocyte activation-induced epidermal hyperplasia and cytokine-mediated inflammation. We demonstrated in our previous study that CCN1 promoted keratinocyte activation in psoriasis. However, the role of CCN1 in regulating inflammation in psoriasis is still unknown. Here, we showed that CCN1 increased inflammatory cytokine IL-1β production in keratinocytes. Furthermore, endogenous ATP and caspase-1 were required for mature IL-1β production stimulated by CCN1 in keratinocytes. After binding to the receptor of integrin α6β1, CCN1 activated the downstream p38 MAPK signaling pathway, thus inducing the expression of IL-1β. In addition, we inhibited CCN1 function in mouse models of psoriasis, and decreased IL-1β production was observed in vivo. Overall, we showed that CCN1 increased IL-1β production via p38 MAPK signaling, indicating a role for CCN1 protein in regulating inflammation in psoriasis.
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