Cytokine/Chemokine Secretion and Proteomic Identification of Upregulated Annexin A1 from Peripheral Blood Mononuclear Cells Cocultured with the Liver Fluke Opisthorchis viverrini

Hongsrichan, Nuttanan; Intuyod, Kitti; Pinlaor, Porntip; Khoontawad, Jarinya; Yongvanit, Puangrat; Wongkham, Chaisiri; Roytrakul, Sittiruk; Pinlaor, Somchai

doi:10.1128/iai.00901-13

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…However, the secretion of cytokine/chemokines in BECs, which might interact closely with C. sinensis as well as its ESP, is unknown and the roles of TLR4 in inflammatory responses in the BECs stimulated by ESP of C. sinensis remains to be covered. In the present study, we found that TNF-α but not IL-6 were significantly increased in the supernatant of cultured MIBECs stimulated by ESP of C. sinensis for 48 h, suggesting that BEC might play a crucial role in immunoregulation and immune responses to C. sinensis infection since TNF-α can potently regulate immune responses and induce nitric oxide, which lead to the parasites death and the healing of damaged tissues [ 30 , 31 ]. Surprisingly, IL-6 secreted by MIBECs could not be significantly triggered by ESP of C. sinensis , however, when MIBECs co-stimulated by ESP and LPS, the levels of IL-6 in cultured supernatant of MIBECs were statistically decreased, compared with those stimulated by LPS alone (Fig.…”

Section: Resultsmentioning

confidence: 99%

Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4

Yan

Wang

et al. 2015

Parasites Vectors

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BackgroundToll-like receptor 4 (TLR4), as one of the most important pathogen pattern recognitions (PPRs) plays a central role in elicitation of innate immunity and mediation of adaptive responses against foreign antigens. However, little is known of the roles of TLR4 in the immune responses of biliary epithelial cells (BECs) induced by Clonorchis sinensis, a parasite of significance in human health.MethodsIn the present study, the primary mouse intrahepatic biliary epithelial cells (MIBECs) were pre-treated with TLR4 inhibitor peptide or control peptide and then stimulated by excretory/secretory products (ESP) of C. sinensis, respectively. The expressions of TLR4 and relative cytokines were determined using western blot and a bead-based analytic detection system, respectively.ResultsThe results showed that ESP of C. sinensis significantly increased the expression of TLR4 which promoted the expression of MyD88 and NF-κB in BECs; the levels of TNF-α but not IL-6 from MIBECs stimulated by ESP alone were also considerably increased, compared with the group of the medium stimulated. However, the concentration of TNF-α was significantly decreased when MIBECs were pre-treated with TLR4 inhibitor. In addition, ESP could depress the level of IL-6 in MIBECs which was elevated by LPS.ConclusionsOur data for the first time demonstrate that ESP of C. sinensis can potently induce secretion of pro-inflammatory cytokines via TLR4 in MIBECs, which suggests that TLR4 plays an important role in host defenses against C. sinensis and the pathogenesis of clonorchiasis.

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Section: Resultsmentioning

confidence: 99%

Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4

Yan

Wang

et al. 2015

Parasites Vectors

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“…During the co-occurrence of opisthorchiasis and diabetes, Il-6 , Il-12 and Il-13 were dominantly increased. Expression levels of the inhibitory cytokines Il-10 and Tgf-β were generally unaffected during infection and/or diabetes, likely reflecting the impairment of immune response in diabetes [ 44 ] and participation of the cytokines in pathogenesis during liver fluke infection [ 22 , 45 ]. Liver fibrosis is associated with upregulation of Tgf-β [ 46 ] and biliary periductal fibrosis and increased levels of Il-6 characterize chronic opisthorchiasis [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Metacercariae that did not exhibit larval movements were discarded. Hamsters were infected by stomach intubation with 50 viable metacercariae [ 10 , 45 ]. Hamsters in the OD group were infected with the metacercariae after occurrence of diabetes (FBG ≥ 250 mg/dL).…”

Section: Methodsmentioning

confidence: 99%

Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the hepatobiliary tract disease

et al. 2018

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Complications arising from infection with the carcinogenic liver fluke Opisthorchis viverrini cause substantial morbidity and mortality in Thailand and adjacent lower Mekong countries. In parallel, the incidence rate of diabetes mellitus (DM) is increasing in this same region, and indeed worldwide. Many residents in opisthorchiasis-endemic regions also exhibit DM, but the hepatobiliary disease arising during the co-occurrence of these two conditions remains to be characterized. Here, the histopathological profile during co-occurrence of opisthorchiasis and DM was investigated in a rodent model of human opisthorchiasis in which diabetes was induced with streptozotocin. The effects of excretory/secretory products from the liver fluke, O. viverrini (OVES) on hepatocyte and cholangiocyte responses during hyperglycemic conditions also were monitored. Both the liver fluke-infected hamsters (OV group) and hamsters with DM lost weight compared to control hamsters. Weight loss was even more marked in the hamsters with both opisthorchiasis and DM (OD group). Hypertrophy of hepatocytes, altered biliary canaliculi, and biliary hyperplasia were more prominent in the OD group, compared with OV and DM groups. Profound oxidative DNA damage, evidenced by 8-oxo-2'-deoxyguanosine, proliferating cell nuclear antigen, and periductal fibrosis characterized the OD compared to OV and DM hamsters. Upregulation of expression of cytokines in response to infection and impairment of the pathway for insulin receptor substrate (IRS)/phosphatidylinositol-3-kinases (PI3K)/protein kinase B (AKT) signaling attended these changes. In vitro, OVES and glucose provoked time- and dose-dependent effects on the proliferation of both hepatocytes and cholangiocytes. In overview, the co-occurrence of opisthorchiasis and diabetes exacerbated pathophysiological damage to the hepatobiliary tract. We speculate that opisthorchiasis and diabetes together aggravate hepatobiliary pathogenesis through an IRS/PI3K/AKT-independent pathway.

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“…Table 2c), including 50 of the 92 proteins that had been identified as dysregulated in both experimental groups when compared to the normal controls. Many of these 50 proteins, for example vimentin and annexin A1 [30], have been associated with different malignancies which, when combined with the very similar enriched GO terms from the 'Ov-induced CCA' and 'Ov-infected' groups, suggests that some protein expression changes associated with cancer are occurring during infection and that increased expression of these proteins could mark the transition from infection to CCA.…”

Section: Proteins Dysregulated During Ov Infection and Ov-induced Ccamentioning

confidence: 94%

Differential protein expression marks the transition from infection withOpisthorchis viverrinito cholangiocarcinoma

Khoontawad

Pairojkul

Rucksaken

et al. 2016

Preprint

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Running title: Differential protein expression marks the transition to CCA 2 Abbreviations CCA, cholangiocarcinoma; Ov, Opisthorchis viverrini; NDMA, N-nitrosodimethylamine; IHC, immunohistochemistry MMTS, methyl methanethiosulfonate TPP, Trans Proteomic Pipeline 3 SummaryParts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world due to infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labelling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected but not cancerous) versus cancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue.We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA, i.e. proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared to proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer. 4

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Cytokine/Chemokine Secretion and Proteomic Identification of Upregulated Annexin A1 from Peripheral Blood Mononuclear Cells Cocultured with the Liver Fluke Opisthorchis viverrini

Cited by 12 publications

References 43 publications

Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4

Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4

Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the hepatobiliary tract disease

Differential protein expression marks the transition from infection withOpisthorchis viverrinito cholangiocarcinoma

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