title: CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis.
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.
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tianhang
authors.initials: T
authors.lastname: Zhai
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Haichuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rongfen
authors.initials: R
authors.lastname: Huo
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Baihua
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Beiqing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Teng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism*; D004195:Disease Models, Animal; D039121:Integrin alpha6beta1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D015603:Keratinocytes / Q000473:pathology*; D051379:Mice; D011485:Protein Binding; D011565:Psoriasis / Q000473:pathology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C491850:CCN1 protein, mouse; D055515:Cysteine-Rich Protein 61; D039121:Integrin alpha6beta1; D053583:Interleukin-1beta; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1