title: Alteration of intracellular secretory acute phase response proteins expressed in human hepatocyte induced by exposure with interleukin-6.
abstract: Interleukin-6 (IL-6) is a principal proinflammatory cytokine inducing the acute phase response in various tissues, including liver. Here, we adopt the FD-LC-MS/MS method, consisting of fluorogenic derivatization (FD), separation by liquid chromatography (LC), and identification of proteins by LC-tandem mass spectrometry (MS/MS), to reveal how exposure to IL-6 alters temporally the intracellular secretory acute phase response (sAPR) proteins expressed in human hepatocytes as compared to non-exposure. Nine altered sAPR proteins were identified in cultures in response to IL-6. Seven of them (serum amyloid A protein, haptoglobin, fibrinogen α chain, fibrinogen β chain, fibrinogen γ chain, α(1)-acid glycoprotein and α(1)-antitrypsin) were significantly increased and two (β(2)-glycoprotein 1 and transferrin) were significantly decreased in response to IL-6. In addition, the transmission speed of transferrin might be much faster than the other sAPR proteins. These results suggest a different molecular mechanism for protein synthesis and the secretory pathway among the sAPR proteins. In this study, we observed the simultaneously and temporally altered expression of sAPR proteins which had been induced by exposure to IL-6 in human hepatocytes, in contrast to previous reports, in all of which the proteins were tested from the time they were secreted into the medium from the cells.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-Shi, Tokyo 202-8585, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nakata
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Saitoh
authors.forename: Jun
authors.initials: J
authors.lastname: Amano
authors.forename: Akiyo
authors.initials: A
authors.lastname: Koshiyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichibangase
authors.forename: Naoaki
authors.initials: N
authors.lastname: Murao
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ohta
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aso
authors.forename: Masaki
authors.initials: M
authors.lastname: Ishigai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imai
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000210:Acute-Phase Reaction / Q000378:metabolism*; D015153:Blotting, Western; D002853:Chromatography, Liquid; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D006242:Haptoglobins / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D013058:Mass Spectrometry; D008875:Middle Aged; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D005456:Fluorescent Dyes; D006242:Haptoglobins; D015850:Interleukin-6