Korean J Parasitol.  2016 Oct;54(5):679-684. 10.3347/kjp.2016.54.5.679.

Toll-Like Receptor-Mediated Free Radical Generation in Clonorchis sinensis Excretory-Secretory Product-Treated Cholangiocarcinoma Cells

• Bahk YY
• Pak JH

• KMID: 2360534
• DOI: http://doi.org/10.3347/kjp.2016.54.5.679

Abstract

Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-κB-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

Keyword

Clonorchis sinensis; Toll-like receptor (TLR); free radical; excretory-secretory product (ESP); cholangiocarcinoma cell line

MeSH Terms

Antibodies
Bile Ducts
Cholangiocarcinoma*
Clonorchiasis
Clonorchis sinensis*
Free Radicals
Humans
Immunity, Innate
Inflammation
RNA, Messenger
Signal Transduction
Toll-Like Receptors
Antibodies
Free Radicals
RNA, Messenger
Toll-Like Receptors