title: Opisthorchis viverrini-antigen induces expression of MARCKS during inflammation-associated cholangiocarcinogenesis.
abstract: Myristoylated alanine rich C kinase substrate (MARCKS) has been implicated in PKC-mediated membrane-cytoskeleton alterations that underlie lipopolysaccharide (LPS)-induced macrophage responses. MARCKS is postulated to be involved in inflammation-associated CCA based on its overexpression in cholangiocarcinoma (CCA) and inflammatory cells. The aims of this study were to investigate localization patterns of MARCKS in hamster and human tissue during cholangiocarcinogenesis and to examine the involvement of MARCKS in inflammation. MARCKS protein expression was found prominently in inflammatory cells of Opisthorchis viverrini-treated as well as O. viverrini plus N-nitrosodimethylamine (NDMA)-treated hamsters from week 2 to week 3 of treatment. The positive signal decreased during week 4 to week 12, then increased again at week 26 when CCA developed. At the last time point the expression of MARCKS was observed in both cancer and inflammatory cells. MARCKS protein expression was also found in inflammatory cells, including macrophages in human CCA tissues. O. viverrini excretory/secretory products or worm antigen induced MARCKS mRNA and protein expression in a dose- and time-dependent manner in the human U937 macrophage cell line. The relative mRNA expression of MARCKS in white blood cells of O. viverrini-infected patients was significantly higher than in healthy subjects (P = 0.02). Thus, MARCKS is significantly expressed in macrophages and plays a role in inflammation-related CCA induced by O. viverrini.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.forename: Kunyarat
authors.initials: K
authors.lastname: Duenngai
authors.forename: Ubon
authors.initials: U
authors.lastname: Cha'on
authors.forename: Raynoo
authors.initials: R
authors.lastname: Thanan
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000469:parasitology / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000469:parasitology / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D006224:Cricetinae; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000469:parasitology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008647:Mesocricetus; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009889:Opisthorchiasis / Q000150:complications / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D009891:Opisthorchis / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D020298:U937 Cells / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
chemical_list: D000947:Antigens, Helminth; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D004128:Dimethylnitrosamine