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

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• 作者：Kantima Ninlawan ; Steve P. O'Hara ; Patrick L. Splinter ; Puangrat Yongvanit ; Sasithorn Kaewkes ; Arpa Surapaitoon ; Nicholas F. LaRusso ; Banchob Sripa
• 关键词：Opisthorchis viverrini excretory/secretory products ; Cholangiocyte ; Toll-like receptors ; NF-κ ; B ; Cytokines
• 刊名：Parasitology International
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：59
• 期：4
• 页码：616-621
• 全文大小：711 K

文摘

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.