title: Toll-Like Receptor-Mediated Free Radical Generation inClonorchis sinensisExcretory-Secretory Product-Treated Cholangiocarcinoma Cells.
abstract: Clonorchiasis, caused by direct contact withClonorchis sinensisworms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated byC. sinensisESPs cause NF-κB-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiatingC. sinensisinfection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 27478, Korea.
authors.forename: Young Yil
authors.initials: YY
authors.lastname: Bahk
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D045744:Cell Line, Tumor; D003004:Clonorchis sinensis / Q000276:immunology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D000947:Antigens, Helminth; D005609:Free Radicals; D051193:Toll-Like Receptors
keywords: Clonorchis sinensis; Toll-like receptor (TLR); cholangiocarcinoma cell line; excretory-secretory product (ESP); free radical