Increased expression of TLR-2, COX-2, and SOD-2 genes in the peripheral blood leukocytes of opisthorchiasis patients induced by Opisthorchis viverrini antigen

Yongvanit, Puangrat; Thanan, Raynoo; Pinlaor, Somchai; Sithithaworn, Paiboon; Loilome, Watcharin; Namwat, Nisana; Techasen, Anchalee; Dechakhamphu, Ananya

doi:10.1007/s00436-011-2725-5

Cited by 16 publications

(8 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results of present study showed that the transcripts of both TLR2 and TLR4 gene were increased on day 28 PI, which is interestingly consistent with the increased in cytokines including Th1 and Th2 types immune responses, suggesting that TLR2 and TLR4 might be engaged in the production of cytokines such as IL-4, IL-10, IFN-γ, and TNF-α in mice with C. sinensis infection [36]. In addition, TLR2-mediated immune response via inflammatory/anti-inflammatory cytokines may be involved in the imbalance of oxidants/antioxidants in patients re-infected by O. viverrini [37].…”

Section: Discussionsupporting

confidence: 62%

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Yan

et al. 2015

J Infect Dev Ctries

View full text Add to dashboard Cite

Introduction: Clonorchis sinensis is one of the most important foodborne pathogens in humans, and can cause biliary diseases such as gallstones, cholecystitis, cholangitis, and cholangiocarcinoma. Toll-like receptors (TLRs) as sensors are crucial to initiating both innate and adaptive immune defenses against pathogens. However, little is known about the hepatic expression of TLRs of hosts induced by C. sinensis infection. Methodology: In the present study, the expression and distribution of TLR2 and TLR4 were investigated in a mouse model of clonorchiasis on days 28, 56, 84, and 112 post-infection (PI) using real-time quantitative reverse transcription polymerase chain reaction (PCR) and immunohistochemically staining, respectively. The levels of cytokines that are mediated by TLR2 and TLR4 were also evaluated using a cytometric bead array. Results: Results showed that the transcripts of TLR2 and TLR4 were upregulated on day 28 PI in C. sinensis-infected mice compared with non-infected ones (p < 0.01). In addition, their proteins were strongly immunohistochemically positive in the cytoplasm and membrane of endothelial cells, fibroblasts, and biliary epithelium cells of C. sinensis-infected mice. The levels of interleukin (IL)-4, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were increased with activation of TLR2 and TLR4. Conclusions: The expression of TLR2 and TLR4 is upregulated against C. sinensis infection, which suggests that TLR2 and TLR4 might be involved in immune responses during C. sinensis infection.

show abstract

Section: Discussionsupporting

confidence: 62%

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Yan

et al. 2015

J Infect Dev Ctries

View full text Add to dashboard Cite

show abstract

“…Re-infection of people in endemic areas occurs more likely after praziquantel treatment and frequently leads to periductal fibrosis that governs the pathogenic effects of inflammation and immunity in liver fluke-associated cholangiocarcinogenesis has been recently reviewed ( Yongvanit, Pinlaor & Bartsch, 2012 ). Cellular damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) during chronic infection appears to be a key event which is further enhanced by an imbalanced oxidant/anti-oxidant system during reinfections ( Yongvanit et al, 2012 ). Increase in periductal fibrosis has been shown to be associated with CCA genesis ( Prakobwong et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis

Jamnongkan

Thanee

Yongvanit

et al. 2018

PeerJ

Self Cite

View full text Add to dashboard Cite

Cholangiocarcinoma (CCA) caused by infection of the liver fluke Opisthorchis viverrini, (Ov) is the major public health problem in northeast Thailand. Following Ov infection the subsequent molecular changes can be associated by reactive oxygen species (ROS) induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of cell death in prolonged oxidative stress conditions can occur but some damaged/mutated cells could survive and enable clonal expansion. Our study used a natural product, xanthohumol (XN), which is an anti-oxidant and anti-inflammatory compound, to examine whether it could prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or without praziquantel (PZ), an anti-helminthic treatment, on DNA damage, redox status change including iron accumulation and periductal fibrosis during CCA genesis induced by administration of Ov and N-dinitrosomethylamine (NDMA) in hamsters. Animals were randomly divided into four groups: group I, Ov infection and NDMA administration (ON); group II, Ov infection and NDMA administration and PZ treatment (ONP); the latter 2 groups were similar to group I and II, but group III received additional XN (XON) and group IV received XN plus PZ (XONP). The results showed that high 8-oxodG (a marker of DNA damage) was observed throughout cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the ROS defense system), whereas decreased expression of phospho-p38MAPK (a major ROS target), was found during the progression of the bile duct cell transformation. In addition, high accumulation of iron and expression of transferrin receptor-1 (TfR-1) in both malignant bile ducts and inflammatory cells were detected. Furthermore, fibrosis also increased with the highest level being on day 180. On the other hand, the groups of XN with or without PZ supplementations showed an effective reduction in all the markers examined, including fibrosis when compared with the ON group. In particular, the XONP group, in which a significant reduction DNA damage occurred, was also found to have iron accumulation and fibrosis compared to the other groups. Our results show that XN administered in combination with PZ could efficiently prevent CCA development and hence provide potential chemopreventive benefits in Ov-induced cholangiocarcinogenesis.

show abstract

“…Previously, a significant decrease in the protein expression of manganese-SOD was reported in the cancer cells of CCA tissues, compared with individual normal bile duct cells located in regions adjacent to the tumor (14). Furthermore, the results of our previous study showed that the decreased gene expression of CAT in the peripheral blood leukocytes of patients with opisthorchiasis is induced by Ov antigen (27). Additionally CAT was found to be downregulated in an animal model of opisthorchaiasis-associated CCA, detected via kinetic analysis using the cDNA microarray technique (28).…”

Section: Discussionmentioning

confidence: 96%

Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma

et al. 2016

Self Cite

View full text Add to dashboard Cite

The adaptive response of the genome protection mechanism occurs in cells when exposed to genotoxic stress due to the overproduction of free radicals via inflammation and infection. In such circumstances, cells attempt to maintain health via several genome protection mechanisms. However, evidence is increasing that this adaptive response may have deleterious effect; a reduction of antioxidant enzymes and/or imbalance in the DNA repair system generates microsatellite instability (MSI), which has procarcinogenic implications. Therefore, the present study hypothesized that MSI caused by imbalanced responses of antioxidant enzymes and/or DNA repair enzymes as a result of oxidative/nitrative stress arising from the inflammatory response is involved in liver fluke-associated cholangiocarcinogenesis. The present study investigated this hypothesis by identifying the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), and DNA repair enzymes, including alkyladenine DNA glycosylase (AAG), apurinic endonuclease (APE) and DNA polymerase β (DNA pol β). In addition, the activities of the antioxidant enzymes, SOD2 and CAT, were examined in human cholangiocarcinoma (CCA) tissues using immunohistochemical staining. MSI was also analyzed in human CCA tissues. The resulting data demonstrated that the expression levels of the SOD2 and CAT enzymes decreased. The activities of SOD2 and CAT decreased significantly in the CCA tissues, compared with the hepatic tissue of cadaveric donors. In the DNA repairing enzymes, it was found that the expression levels of AAG and DNA pol β enzymes increased, whereas the expression of APE decreased. In addition, it was found that MSI-high was present in 69% of patients, whereas MSI-low was present in 31% of patients, with no patients classified as having microsatellite stability. In the patients, a MSI-high was correlated with poor prognosis, indicated by a shorter survival rate. These results indicated that the reduction of antioxidant enzymes and adaptive imbalance of base excision repair enzymes in human CCA caused MSI, and may be associated with the progression of cancer.

show abstract

Increased expression of TLR-2, COX-2, and SOD-2 genes in the peripheral blood leukocytes of opisthorchiasis patients induced by Opisthorchis viverrini antigen

Cited by 16 publications

References 32 publications

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis

Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma

Contact Info

Product

Resources

About