During chronic opisthorchiasis, pathogenesis is manifested in a series of well-defined stages as the normal tissue architecture of the biliary epithelium is progressively remodeled by the chronic inflammatory response from repeated injury sustained by the biliary epithelium from a combination ofthe mechanical, toxic, and immune mechanisms of the fluke in the bile duct. As individuals are infected with O. viverrini for many years (often a lifetime), a persistent cycle of tissue damage and repair takes place in the intrahepatic biliary ducts, creating a chronic inflammatory milieu that stimulates periductal fibrogenesis and provides the """"""""smoldering and polarized"""""""" inflammatory basis for malignant transformation of biliary epithelial cells to cholangiocarcinoma (CCA). In project 1, we hypothesize the existence of a pro-inflammatory phenotype which is characterized by a inflammatory cytokine dysregulation such that, even after removal ofthe pathogen by PZQ, individuals with the pro-inflammatory phenotype continue to produce high levels of IL-6 and an unreversed (i.e., persistent) form of Advanced Periductal Fibrosis (APF). We further hypothesize that this persistent APF provides the basis for malignant transformation to CCA. Project 1 ofthe TMRC will focus on the processes involved in this chronic inflammatory phenotype and the progression from infection to persistent APF and eventually to malignant transformation (CCA) by undertaking the following specific aims: (1) continuing our a community-based cohort study for the risk factors associated with Advanced Periductal Fibrosis in villages with high O. viverrini transmission along the Chi River basin in Khon Kaen, Thailand to stratify infected individuals into those with """"""""resolved"""""""" and """"""""persistent"""""""" Advanced Periductal Fibrosis;(2) to determine the host inflammatory cytokine signaling pathways, such as the IL-6 signaling pathways, induced during chronic O. viverrini infection on the risk of progressing either resolved or persistent advanced periductal fibrosis, and bile duct cancer;and (3) examine the genetic diversity ofthe O. viverrini parasite by microsatellite DNA analysis and its association with resolved and persistent forms advanced periductal fibrosis. .
Individuals residents in O. viverrini endemic areas can remain infected for a lifetime. However, only 25% of O. viverrini-infected individuals develop periductal fibrosis and 1 % progress to CCA. The observation that individuals living under similar transmission conditions show differing rates of APF and CCA indicates a strong role for diverse host and parasite factors in the disease process.
|Surapaitoon, Arpa; Suttiprapa, Sutas; Khuntikeo, Narong et al. (2017) Cytokine profiles in Opisthorchis viverrini stimulated peripheral blood mononuclear cells from cholangiocarcinoma patients. Parasitol Int 66:889-892|
|Surapaitoon, Arpa; Suttiprapa, Sutas; Mairiang, Eimorn et al. (2017) Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma. Korean J Parasitol 55:295-304|
|Deenonpoe, Raksawan; Mairiang, Eimorn; Mairiang, Pisaln et al. (2017) Elevated prevalence of Helicobacter species and virulence factors in opisthorchiasis and associated hepatobiliary disease. Sci Rep 7:42744|
|Potriquet, Jeremy; Laohaviroj, Marut; Bethony, Jeffrey M et al. (2017) A modified FASP protocol for high-throughput preparation of protein samples for mass spectrometry. PLoS One 12:e0175967|
|van Tong, Hoang; Brindley, Paul J; Meyer, Christian G et al. (2017) Parasite Infection, Carcinogenesis and Human Malignancy. EBioMedicine 15:12-23|
|Kim, Christina Sunyoung; Smith, John F; Suwannatrai, Apiporn et al. (2017) Role of socio-cultural and economic factors in cyprinid fish distribution networks and consumption in Lawa Lake region, Northeast Thailand: Novel perspectives on Opisthorchis viverrini transmission dynamics. Acta Trop 170:85-94|
|Vinh, Hoang Quang; Phimpraphai, Waraphon; Tangkawattana, Sirikachorn et al. (2017) Risk factors for Clonorchis sinensis infection transmission in humans in northern Vietnam: A descriptive and social network analysis study. Parasitol Int 66:74-82|
|Echaubard, Pierre; León, Tomas; Suwanatrai, Kulwadee et al. (2017) Experimental and modelling investigations of Opisthorchis viverrini miracidia transmission over time and across temperatures: implications for control. Int J Parasitol 47:257-270|
|Khoontawad, Jarinya; Pairojkul, Chawalit; Rucksaken, Rucksak et al. (2017) Differential Protein Expression Marks the Transition From Infection With Opisthorchis viverrini to Cholangiocarcinoma. Mol Cell Proteomics 16:911-923|
|Van, Chinh Dang; Doungchawee, Galayanee; Suttiprapa, Sutas et al. (2017) Association between Opisthorchis viverrini and Leptospira spp. infection in endemic Northeast Thailand. Parasitol Int 66:503-509|
Showing the most recent 10 out of 42 publications