Opisthorchis viverrini excretory/secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte.
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.
Ninlawan
Kantima
K
Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.
O'Hara
Steve P
SP
Splinter
Patrick L
PL
Yongvanit
Puangrat
P
Kaewkes
Sasithorn
S
Surapaitoon
Arpa
A
LaRusso
Nicholas F
NF
Sripa
Banchob
B
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
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