Opisthorchis viverrini excretory/secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte

Kantima Ninlawan, Steve P. O'Hara, Patrick L. Splinter, Puangrat Yongvanit, Sasithorn Kaewkes, Arpa Surapaitoon, Nicholas F. LaRusso, Banchob Sripa

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)616-621
Number of pages6
JournalParasitology International
Volume59
Issue number4
DOIs
StatePublished - Dec 1 2010

    Fingerprint

Keywords

  • Cholangiocyte
  • Cytokines
  • Opisthorchis viverrini excretory/secretory products
  • Toll-like receptors, NF-ΚB

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this