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CCN1 promotes IL-1? 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-1? production in keratinocytes. Furthermore, endogenous ATP and caspase-1 were required for mature IL-1? production stimulated by CCN1 in keratinocytes. After binding to the receptor of integrin ?6?1, CCN1 activated the downstream p38 MAPK signaling pathway, thus inducing the expression of IL-1?. In addition, we inhibited CCN1 function in mouse models of psoriasis, and decreased IL-1? production was observed in vivo. Overall, we showed that CCN1 increased IL-1? production via p38 MAPK signaling, indicating a role for CCN1 protein in regulating inflammation in psoriasis.

SUBMITTER: Sun Y

PROVIDER: S-EPMC5339692 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis.

Sun Yue Y Zhang Jie J Zhai Tianhang T Li Huidan H Li Haichuan H Huo Rongfen R Shen Baihua B Wang Beiqing B Chen Xiangdong X Li Ningli N Teng Jialin J

Scientific reports 20170307

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, ...[more]

PMID: 28266627

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Project description:Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1β on the changes that can promote VM. The evidence for VM stimulated by IL-1β was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-β. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1β treatment. The increase in VM response was observed in IL-1β treated cells under both normoxia and hypoxia. IL-1β also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1β stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1β stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1β may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells.

Dataset Information

CCN1 promotes IL-1? production in keratinocytes by activating p38 MAPK signaling in psoriasis.

Publications

CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis.

Similar Datasets

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