title: M1-/M2-macrophage polarization in pseudolobules consisting of adipohilin-rich hepatocytes in thioacetamide (TAA)-induced rat hepatic cirrhosis.
abstract: Liver steatosis is the most frequent liver disease and may further develop into non-alcoholic steatohepatitis (NASH), liver cirrhosis, and finally hepatocellular carcinoma. Adipophilin (Adp) is localized on lipid droplet membrane in cytoplasm, and its increased expression is related to development of steatosis and NASH. The relationship between M1-/M2-macrophage polarization and Adp-rich hepatocyte-consisting pseudolobules (PLs) was investigated in thioacetamide (TAA)-induced rat cirrhosis.
  
  
  
  F344 rats were injected twice weekly with TAA (100mg/kg bodyweight) and sacrificed at post-first injection (PFI) weeks 5, 10, 15, 20, 25 and 32. Macrophage immunophenotypes and Adp-containing hepatocytes were analyzed by single immunolabeling. Adp and M1-/M2-related factors were analyzed by real -time RT-PCR.
  
  
  
  PLs consisting exclusively of Adp-containing hepatocytes (Adp-positive) and PLs consisting of few Adp-containing hepatocytes (Adp-negative) were clearly distinguishable at PFI week 20 onwards. The numbers of M1-macrophages (reacting to CD68 and Iba1) and M2- macrophages (reacting to CD163, CD204 and Gal-3) were considerably greater in Adp-positive PLs. Expressions for both M1 (TNF-α, MCP-1, and Iba1)- and M2 (IL-4, TGF-β1, Gal-3, and Hsp25)-related factors were markedly higher in Adp-positive PLs at PFI week 25. Interestingly, MHC class II-positive macrophages/dendritic cells were increased in Adp-positive clusters/foci at the early stages at PFI weeks 5 and 10, and the level was gradually decreased thereafter.
  
  
  
  M1-/M2-macrophages may simultaneously participate in the pathogenesis of steatosis in TAA-induced cirrhosis through M1- and M2-related factors. MHC class II cells may be responsible for steatosis at early stages, suggesting different functions from the above M1-/M2-macropahges.
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan; Veterinary Pathology, Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Sri Lanka, 20000.
authors.forename: Kavindra Kumara
authors.initials: KK
authors.lastname: Wijesundera
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan; Teaching Hospital Peradeniya, Peradeniya, 20400, Sri Lanka.
authors.forename: Anusha Hemamali
authors.initials: AH
authors.lastname: Tennakoon
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Hossain Md
authors.initials: HM
authors.lastname: Golbar
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Miyuu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan. Electronic address: yamate@vet.osakafu-u.ac.jp.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D016764:Cell Polarity; D049109:Cell Proliferation; D037502:Galectin 3 / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007700:Kinetics; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D000070780:Perilipin-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011916:Rats, Inbred F344; D013853:Thioacetamide
chemical_list: D015703:Antigens, CD; D037502:Galectin 3; D000070780:Perilipin-2; D012333:RNA, Messenger; D013853:Thioacetamide
keywords: Adipophilin; F344 rats; Macrophage polarization; Thioacetamide