title: Opisthorchis viverrini excretory/secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte.
abstract: Biliary tract infection with the Group I carcinogenic liver fluke Opisthorchis viverrini is associated with severe inflammation leading to cholangiocarcinoma--a major biliary cancer in Southeast Asia. However, mechanism(s) by which the liver fluke induces host mucosal immune/inflammatory responses is unclear. In the present study we address whether a normal immortalized human cholangiocyte cell line (H69 cells) recognizes and responds to O. viverrini excretory/secretory products (OVES). Expression of multiple TLRs, activation of NF-κB, and expression of pro-inflammatory cytokines were monitored in the presence and absence of OVES. Our results showed that OVES induced increased cholangiocyte TLR4 mRNA expression, induced IκB-α degradation in a MyD88-dependent manner, and activated NF-κB nuclear translocation. Moreover, OVES induced expression and secretion of the strong chemoattractant chemokine interleukin 8 (IL-8) and pro-inflammatory cytokine IL-6. These results demonstrate that secreted/excreted products of O. viverrini are recognized by human cholangiocytes and initiate innate mucosal immunity/inflammatory cascades, a primary event in the pathogenesis of opisthorchiasis and cholangiocarcinoma.
authors.affiliation: Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Kantima
authors.initials: K
authors.lastname: Ninlawan
authors.forename: Steve P
authors.initials: SP
authors.lastname: O'Hara
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Splinter
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Sasithorn
authors.initials: S
authors.lastname: Kaewkes
authors.forename: Arpa
authors.initials: A
authors.lastname: Surapaitoon
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: LaRusso
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000276:immunology*; D002461:Cell Line, Transformed; D018281:Cholangiocarcinoma / Q000276:immunology / Q000503:physiopathology; D006224:Cricetinae; D004847:Epithelial Cells / Q000276:immunology; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009889:Opisthorchiasis / Q000276:immunology / Q000503:physiopathology; D009891:Opisthorchis / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015801:Helminth Proteins; D015850:Interleukin-6; D016209:Interleukin-8; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4