title: Clonorchis sinensis ferritin heavy chain triggers free radicals and mediates inflammation signaling in human hepatic stellate cells.
abstract: Clonorchiasis, caused by direct and continuous contact with Clonorchis sinensis, is associated with hepatobiliary damage, inflammation, periductal fibrosis, and the development of cholangiocarcinoma. Hepatic stellate cells respond to liver injury through production of proinflammatory mediators which drive fibrogenesis; however, their endogenous sources and pathophysiological roles in host cells were not determined. C. sinensis ferritin heavy chain (CsFHC) was previously confirmed as a component of excretory/secretory products and exhibited a number of extrahepatic immunomodulatory properties in various diseases. In this study, we investigated the expression pattern and biological role of CsFHC in C. sinensis. CsFHC was expressed throughout life stages of C. sinensis. More importantly, we found that treatment of human hepatic stellate cell line LX-2 with CsFHC triggered the production of free radicals via time-dependent activation of NADPH oxidase, xanthine oxidase, and inducible nitric oxide synthase. The increase in free radicals substantially promoted the degradation of cytosolic IκBα and nuclear translocation of NF-κB subunits (p65 and p50). CsFHC-induced NF-κB activation was markedly attenuated by preincubation with specific inhibitors of corresponding free radical-producing enzyme or the antioxidant. In addition, CsFHC induced an increased expression level of proinflammatory cytokines, IL-1β and IL-6, in NF-κB-dependent manner. Our results indicate that CsFHC-triggered free radical-mediated NF-κB signaling is an important factor in the chronic inflammation caused by C. sinensis infection.
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Mao
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Xie
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chen
authors.forename: Mengyu
authors.initials: M
authors.lastname: Ren
authors.forename: Mei
authors.initials: M
authors.lastname: Shang
authors.forename: Huali
authors.initials: H
authors.lastname: Lei
authors.forename: Yanli
authors.initials: Y
authors.lastname: Tian
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Pei
authors.initials: P
authors.lastname: Liang
authors.forename: Tingjin
authors.initials: T
authors.lastname: Chen
authors.forename: Chi
authors.initials: C
authors.lastname: Liang
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Xuerong
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Xinbing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000378:metabolism*; D002460:Cell Line; D003003:Clonorchiasis / Q000276:immunology* / Q000469:parasitology; D003004:Clonorchis sinensis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D005609:Free Radicals; D016328:NF-kappa B; D011994:Recombinant Proteins; D001052:Apoferritins