TY - JOUR
T1 - Opisthorchis viverrini excretory/secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte
AU - Ninlawan, Kantima
AU - O'Hara, Steve P.
AU - Splinter, Patrick L.
AU - Yongvanit, Puangrat
AU - Kaewkes, Sasithorn
AU - Surapaitoon, Arpa
AU - LaRusso, Nicholas F.
AU - Sripa, Banchob
N1 - Funding Information:
This work was supported by the National Research Council of Thailand (NRCT) , the Thailand Research Fund (TRF grant no. BRG4580016 ), the National Institutes of Health Grant DK57993 (N.F.L), and in part, by the NIH-NIAID (award number 1UO1 AI065871 ). Kantima Ninlawan is a Royal Golden Jubilee PhD Scholar through Dr. Banchob Sripa.
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - Cholangiocyte
KW - Cytokines
KW - Opisthorchis viverrini excretory/secretory products
KW - Toll-like receptors, NF-ΚB
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U2 - 10.1016/j.parint.2010.09.008
DO - 10.1016/j.parint.2010.09.008
M3 - Article
C2 - 20887801
AN - SCOPUS:77958453560
SN - 1383-5769
VL - 59
SP - 616
EP - 621
JO - Parasitology International
JF - Parasitology International
IS - 4
ER -