Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Cytokine Production in Cholangiocarcinoma Cells in Response to Clonorchis sinensis Excretory-Secretory Products and Their Putative Protein Components

  • Pak, Jhang Ho (Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center) ;
  • Lee, Ji-Yun (Department of Medical Environmental Biology, Chung-Ang University College of Medicine) ;
  • Jeon, Bo Young (Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center) ;
  • Dai, Fuhong (Department of Medical Environmental Biology, Chung-Ang University College of Medicine) ;
  • Yoo, Won Gi (Department of Medical Environmental Biology, Chung-Ang University College of Medicine) ;
  • Hong, Sung-Jong (Department of Medical Environmental Biology, Chung-Ang University College of Medicine)
  • Received : 2019.07.04
  • Accepted : 2019.08.01
  • Published : 2019.08.31
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Abstract

Clonorchis sinensis is a carcinogenic human liver fluke that promotes hepatic inflammatory environments via direct contact or through their excretory-secretory products (ESPs), subsequently leading to cholangitis, periductal fibrosis, liver cirrhosis, and even cholangiocarcinoma (CCA). This study was conducted to examine the host inflammatory responses to C. sinensis ESPs and their putative protein components selected from C. sinensis expressed sequenced tag (EST) pool databases, including $TGF-{\beta}$ receptor interacting protein 1(CsTRIP1), legumain (CsLeg), and growth factor binding protein 2 (CsGrb2). Treatment of CCA cells (HuCCT1) with the ESPs or bacterial recombinant C. sinensis proteins differentially promoted the secretion of proinflammatory cytokines ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) as well as anti-inflammatory cytokines (IL-10, $TGF-{\beta}1$, and $TGF-{\beta}2$) in a time-dependent manner. In particular, recombinant C. sinensis protein treatment resulted in increase (at maximum) of ~7-fold in $TGF-{\beta}1$, ~30-fold in $TGF-{\beta}2$, and ~3-fold in $TNF-{\alpha}$ compared with the increase produced by ESPs, indicating that CsTrip1, CsLeg, and CsGrb2 function as strong inducers for secretion of these cytokines in host cells. These results suggest that C. sinensis ESPs contribute to the immunopathological response in host cells, leading to clonorchiasis-associated hepatobiliary abnormalities of greater severity.

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