title: Porcine hepatocyte-Kupffer cell co-culture as an in vitro model for testing the efficacy of anti-inflammatory substances.
abstract: As Kupffer cells are highly involved in the regulation of hepatic inflammatory response, the main goal of this study was to improve and to characterize a hepatocyte-Kupffer cell co-culture of pig origin for modelling endotoxin-induced hepatic inflammation and for testing the efficacy of potential anti-inflammatory substances. This monolayer co-culture was prepared from primary isolated swine hepatocytes and Kupffer cells in the ratio of 6:1 and 2:1, mimicking different states of liver inflammation. The prepared cell cultures were characterized by immunohistochemical CD-68 detection. Lipopolysaccharide (LPS) challenge of both co-cultures resulted in elevated interleukin-8 (IL-8) and that of 6:1 co-cultures in increased IL-6 production with a higher extent than on hepatocyte monocultures, justifying the key role of Kupffer cells in pro-inflammatory cytokine production. LPS-induced IL-8 production was successfully attenuated by concomitant application of both sodium butyrate and terpinen-4-ol on hepatocyte monocultures, but not on co-cultures, demonstrating the importance of the presence of Kupffer cells in cell cultures as inflammatory models. Based on these initial data, the applied porcine primary hepatocyte-Kupffer cell co-culture is suggested to be a proper tool for in vitro investigations on liver physiology and hepatic inflammation in pigs and can be used as a useful model mimicking in vivo conditions in veterinary research.
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Mátis
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Kulcsár
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Petrilla
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Talapka
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Neogrády
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000502:physiology*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007728:Kupffer Cells / Q000502:physiology*; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines
keywords: Kupffer cells; butyrate; cytokine; hepatocytes; interleukins; lipopolysaccharide; terpinen-4-ol