Extracellular vesicles of Clonorchis sinensis promote IL-6 and TNF-α secretion via the Toll-like receptor 9-mediated ERK pathway in biliary epithelial cells. (February 2023)

• Record Type: Journal Article
• Authors: Wang, Yuru; Wang, Xiaocen; Zhang, Nan; Yu, Yanhui; Bao, Penglin; Ma, Yeting; Zhang, Haoyang; Zhang, Xu; Zhang, Xichen; Gong, Pengtao; Li, Xin; Li, Jianhua
• Is Part Of: Developmental and comparative immunology. Volume 139(2023)
• Publication Date: 2023-02
• Subjects: Clonorchis sinensis -- Extracellular vesicles -- TLR9 -- ERK pathway -- IL-6 -- TNF-α; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2022.104555
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: Clonorchis sinensis is closely associated with cholangitis, cholecystitis, biliary fibrosis and cholangiocarcinoma. The present study elucidated the role of extracellular vesicles of C. sinensis (CsEVs) in activating Toll-like receptor 9 (TLR9) and regulating inflammatory responses. The results showed that TLR9 expression was increased in the livers of C. sinensis -infected mice. CsEVs were cup-shaped or saucer-shaped and 80–120 nm in diameter. CsEVs activated TLR9 and promoted IL-6 and TNF-α expression in mouse biliary epithelial cells (BECs), and TLR9 siRNA interference reduced the secretion of the two cytokines. CsEV stimulation promoted the phosphorylation of ERK, p38, AKT, and p65, and TLR9 siRNA interference regulated the phosphorylated ERK, AKT and p65 levels. The ERK inhibitor decreased the CsEVs-induced IL-6 and TNF-α secretion. The present study elucidated for the first time that CsEVs induced IL-6 and TNF-α production in BECs via the TLR9-mediated ERK pathway. Graphical abstract: Image 1 Highlights: The extracellular vesicles of Clonorchis sinensi s were isolated and identified. TLR9 can be significantly activated by C. sinensis and CsEVs in vivo and vitro. CsEVs promoted IL-6 and TNF-α secretion via TLR9-ERK pathway in BECs.