title: Lipopolysaccharide blocks induction of unfolded protein response in human hepatoma cell lines.
abstract: In the present study, we examined whether unfolded protein response (UPR) determined the hepatic cell damage induced by an innate immune response including TLR signaling pathways. We observed that lipopolysaccharide (LPS) transcriptionally downregulates 78-kDa glucose-regulated protein/immunoglobulin heavy-chain binding protein (GRP78/Bip), known to confer resistance to apoptosis. We also observed that LPS blocked the induction of UPR and led to poly(ADP-ribose) polymerase (PARP) cleavage in hepatocytes. We also demonstrated that overexpression of GRP78 rescued HepG2 cells treated with LPS from PARP cleavage. These data suggest that UPR downregulation could be a collateral effect of the LPS treatment. We speculate that UPR is an important factor of hepatic cell damage induced by an innate immune response.
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes / Q000235:genetics; D056811:Unfolded Protein Response / Q000187:drug effects / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D011065:Poly(ADP-ribose) Polymerases