title: Acrolein stimulates the synthesis of IL-6 and C-reactive protein (CRP) in thrombosis model mice and cultured cells.
abstract: Measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction with high sensitivity and specificity. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP in thrombosis model mice and cultured cells. In mice with photochemically induced thrombosis, acrolein produced at the locus of infarction increased the level of IL-6 and then CRP in plasma. This was confirmed in cell culture systems - acrolein stimulated the production of IL-6 in mouse neuroblastoma Neuro-2a cells, mouse macrophage-like J774.1 cells, and human umbilical vein endothelial cells (HUVEC), and IL-6 in turn stimulated the production of CRP in human hepatocarcinoma cells. The level of IL-6 mRNA was increased by acrolein through an increase in phosphorylation of the transcription factors, c-Jun, and NF-κB p65. Furthermore, CRP stimulated IL-6 production in mouse macrophage-like J774.1 cells and HUVEC. IL-6 functioned as a protective factor against acrolein toxicity in Neuro-2a cells and HUVEC. These results show that acrolein stimulates the synthesis of IL-6 and CRP, which function as protecting factors against acrolein toxicity, and that the combined measurement of PC-Acro, IL-6, and CRP is effective for identification of silent brain infarction. The combined measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP, and indeed acrolein increased IL-6 synthesis and IL-6 in turn increased CRP synthesis. Furthermore, IL-6 decreased acrolein toxicity in several cell lines.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba, Japan; Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Saiki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hayashi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ikuo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.forename: Itsuko
authors.initials: I
authors.lastname: Ishii
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kan
authors.initials: K
authors.lastname: Chiba
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000171:Acrolein / Q000378:metabolism*; D000818:Animals; D001932:Brain Neoplasms; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002544:Cerebral Infarction / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms; D008264:Macrophages / Q000166:cytology; D051379:Mice; D009447:Neuroblastoma; D013927:Thrombosis / Q000235:genetics* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D051996:Transcription Factor RelA; C577686:interleukin-6, mouse; D000171:Acrolein; D002097:C-Reactive Protein; D048031:JNK Mitogen-Activated Protein Kinases
keywords: CRP; IL-6; NF-κB p65; acrolein; brain infarction; c-Jun