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-kappa B 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 I kappa B-alpha degradation in a MyD88 dependent manner and activated NF-kappa B 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 (C) 2010 Elsevier Ireland Ltd All rights reserved