Alteration of intracellular secretory acute phase response proteins expressed in human hepatocyte induced by exposure with interleukin-6

• Published in: Cytokine (Philadelphia, Pa.) Vol. 59; no. 2; pp. 317 - 323
• Main Authors: Nakata, Katsunori, Saitoh, Ryoichi, Amano, Jun, Koshiyama, Akiyo, Ichibangase, Tomoko, Murao, Naoaki, Ohta, Kunihiro, Aso, Yoshinori, Ishigai, Masaki, Imai, Kazuhiro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2012
• Subjects: Acute phase response protein; Acute-Phase Proteins - secretion; Acute-Phase Reaction - metabolism; amyloid; blood serum; Blotting, Western; Chromatography, Liquid; DAABD-Cl; derivatization; FD-LC-MS/MS method; Female; fibrinogen; Fluorescent Dyes - metabolism; glycoproteins; Haptoglobins - metabolism; hepatocytes; Hepatocytes - drug effects; Hepatocytes - secretion; Human hepatocyte; Humans; Interleukin-6; Interleukin-6 - pharmacology; Intracellular Space - drug effects; Intracellular Space - metabolism; liquid chromatography; liver; Mass Spectrometry; Middle Aged; protein synthesis; Reproducibility of Results; Time Factors; transferrin; DAABD-Cl; Human hepatocyte; LC; FD-LC-MS/MS method; MS/MS; IL-6; FD; Acute phase response protein; Interleukin-6
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2012.04.025

► We adopted the FD-LC-MS/MS method to reveal proteomics response to IL-6. ► The temporal altered expressions of intracellular acute phase proteins were observed. ► Nine altered sAPR proteins were identified in the cells in response to IL-6. ► A mechanism for protein synthesis among the acute phase proteins might be different. ► The transmission of transferrin might be faster than the other acute phase proteins. 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, α1-acid glycoprotein and α1-antitrypsin) were significantly increased and two (β2-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.