title: Peroxiredoxin 6 expression is inversely correlated with nuclear factor-κB activation during Clonorchis sinensis infestation.
abstract: Clonorchis sinensis is a carcinogenic human liver fluke. Its infection promotes persistent oxidative stress and chronic inflammation environments in the bile duct and surrounding liver tissues owing to direct contact with worms and their excretory-secretory products (ESPs), provoking epithelial hyperplasia, periductal fibrosis, and cholangiocarcinogenesis. We examined the reciprocal regulation of two ESP-induced redox-active proteins, NF-κB and peroxiredoxin 6 (Prdx6), during C. sinensis infection. Prdx6 overexpression suppressed intracellular free-radical generation by inhibiting NADPH oxidase2 and inducible nitric oxide synthase activation in the ESP-treated cholangiocarcinoma cells, substantially attenuating NF-κB-mediated inflammation. NF-κB overexpression decreased Prdx6 transcription levels by binding to two κB sites within the promoter. This transcriptional repression was compensated for by other ESP-induced redox-active transcription factors, including erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor 1α (HIF1α), and CCAAT/enhancer-binding protein β (C/EBPβ). Distribution of immunoreactive Prdx6 and NF-κB was distinct in the early stages of infection in mouse livers but shared concomitant localization in the later stages. The intensity and extent of their immunoreactive staining in infected mouse livers are proportional to lesion severity and infection duration. The constitutive elevations of Prdx6 and NF-κB during C. sinensis infection may be associated with more severe persistent hepatobiliary abnormalities mediated by clonorchiasis.
authors.affiliation: Department of Convergence Medicine University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, 388-1 Pungnap-2 dong, Songpa-gu, Seoul 138-736, Republic of Korea. Electronic address: jhpak@amc.seoul.kr.
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Woo Chan
authors.initials: WC
authors.lastname: Son
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
authors.affiliation: Department of Medical Environmental Biology and Research Center for Biomolecules and Biosystems, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sung-Jong
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Department of Parasitology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Woon-Mok
authors.initials: WM
authors.lastname: Sohn
authors.affiliation: Department of Parasitology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
authors.affiliation: Department of Parasitology, Inha University School of Medicine, Incheon 400-103, Republic of Korea.
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000469:parasitology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D003003:Clonorchiasis / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D003004:Clonorchis sinensis / Q000472:pathogenicity* / Q000502:physiology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D000074662:NADPH Oxidase 2 / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2
keywords: Cholangiocarcinoma; Clonorchis sinensis infection; Excretory-secretory products, Prdx6, NF- κB; Free radicals; Redox-active transcription factors