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Korean J Parasitol > Volume 57(4):2019 > Article
The Korean Journal of Parasitology 2019;57(4):379-387. doi: https://doi.org/10.3347/kjp.2019.57.4.379
Cytokine Production in Cholangiocarcinoma Cells in Response to Clonorchis sinensis Excretory-Secretory Products and Their Putative Protein Components
Jhang Ho Pak1, Ji-Yun Lee2, Bo Young Jeon1, Fuhong Dai2,3, Won Gi Yoo2, Sung-Jong Hong2
1Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea
2Department of Medical Environmental Biology, Chung-Ang University College of Medicine, Seoul 06987, Korea
3Department of Parasitology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, 199 Ren-ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, P.R. China
* Corresponding Author: Jhang Ho Pak, Email: jhpak@amc.seoul.kr / Sung-Jong Hong, Email: hongsj@cau.ac.kr
Received: July 4, 2019;  Revised: July 27, 2019;  Accepted: August 1, 2019.
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.
Key words: Clonorchis sinensis, excretory-secretory products, recombinant Cs-driven protein, host immune response, inflammatory cytokine
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