title: A synthetic biotinylated peptide, BP21, inhibits the induction of mRNA expression of inflammatory substances by oxidized- and lyso-phosphatidylcholine.
abstract: Preclinical Research Oxidized low-density lipoprotein (ox-LDL) is implicated in many inflammatory diseases, e.g., type 2 diabetes, obesity, atherosclerosis, and metabolic syndrome. We previously reported that a synthetic biotinylated peptide, BP21, inhibits the bioactivity of ox-LDL via direct binding to ox-LDL. Here, we investigated the effect of BP21 on the mRNA expression of proinflammatory mediators induced by two major components of ox-LDL, oxidized- and lyso-phosphatidylcholine (ox-PC and LPC), in monocytes/macrophages (THP-1 cells) and adipocytes (3T3-L1 cells). In THP-1 cells, BP21 markedly reduced the mRNA expression of interleukin (IL)-6, adipocyte fatty acid-binding protein (aP2), tumor necrosis factor-α, and mitogen-activated protein kinase phosphatase-1, which are induced by one of the major bioactive components of ox-PC, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), and reduced the mRNA expression of IL-6, the ox-LDL-specific scavenger receptor CD36, and aP2 induced by LPC. In adipocytes, the mRNA expression of IL-1β as an adipokine and aP2 is highly induced by ox-PC and LPC, and BP21 markedly reduced the mRNA expression of IL-1β and aP2 induced by POVPC and LPC. Furthermore, BP21 specifically bound to LPC and POVPC in a dose-dependent manner. These results suggest that BP21 may be useful lead for the potential treatment and prevention of inflammatory diseases caused by ox-PC and LPC.
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, Iwaki, Fukushima, 970-8551, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kumagai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ebina
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D019921:Biotinylation; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors*; D008244:Lysophosphatidylcholines / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: C000595069:BP21 peptide; D006460:Hemolysin Proteins; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010446:Peptide Fragments; D010455:Peptides; D010713:Phosphatidylcholines; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D001710:Biotin
keywords: adipocyte; anti-inflammatory drug; biotinylated peptide; inflammation; lysophosphatidylcholine; monocyte/macrophage; oxidized phosphatidylcholine