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Cytokine Production in Cholangiocarcinoma Cells in Response to Clonorchis sinensis Excretory-Secretory Products and Their Putative Protein Components

Korean Journal of Parasitology 2019년 57권 4호 p.379 ~ 387
 ( Pak Jhang-Ho ) - University of Ulsan College of Medicine Asan Medical Center Department of Convergence Medicine

 ( Lee Ji-Yun ) - Chung-Ang University College of Medicine Department of Medical Environmental Biology
 ( Jeon Bo-Young ) - University of Ulsan College of Medicine Asan Medical Center Department of Convergence Medicine
 ( Dai Fuhong ) - Chung-Ang University College of Medicine Department of Medical Environmental Biology
 ( Yoo Won-Gi ) - Chung-Ang University College of Medicine Department of Medical Environmental Biology
 ( Hong Sung-Jong ) - Chung-Ang University College of Medicine Department of Medical Environmental Biology

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-β 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-1β, IL-6, and TNF-α) as well as anti-inflammatory cytokines (IL-10, TGF-β1, and TGF-β2) in a time-dependent manner. In particular, recombinant C. sinensis protein treatment resulted in increase (at maximum) of ~7-fold in TGF-β1, ~30-fold in TGF-β2, and ~3-fold in TNF-α 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.

키워드

Clonorchis sinensis; excretory-secretory products; recombinant Cs-driven protein; host immune response; inflammatory cytokine
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