title: Irbesartan attenuates production of high-mobility group box 1 in response to lipopolysaccharide via downregulation of interferon-β production.
abstract: High-mobility group box 1 (HMGB1) is suggested to participate in development of local and systemic inflammatory disorders. Irbesartan (IRB), an angiotensin II type1 receptor blocker, is widely used for treatment of hypertension, especially in patients with diabetic nephropathy. The effect of IRB on lipopolysaccharide (LPS)-induced HMGB1 and nitric oxide (NO) production was examined using RAW 264.7 macrophage-like cells. IRB inhibited LPS-induced HMGB1 production. IRB also reduced LPS-induced expression of an inducible NO synthase, and inhibited LPS-induced NO production. The expression levels of IFN-β protein and mRNA, which is a key molecule in MyD88-independent pathway of LPS signaling, were exclusively inhibited by IRB. Peroxisome proliferator-activated receptor-γ and angiotensin II type 1 receptor were not involved in the inhibitory action of IRB on LPS-induced HMGB1 and NO production. Collectively, IRB was suggested to inhibit LPS-induced HMGB1 production via downregulation of IFN-β production in the MyD88-independent pathway.
authors: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute Aichi 480-1195, Japan. Electronic address: ykato4@aichi-med-u.ac.jp.
authors: Yoshiro
authors: Y
authors: Kato
authors: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute Aichi 480-1195, Japan.
authors: Hideki
authors: H
authors: Kamiya
authors: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors: Naoki
authors: N
authors: Koide
authors: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors: Erdenezaya
authors: E
authors: Odkhuu
authors: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors: Takayuki
authors: T
authors: Komatsu
authors: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute Aichi 480-1195, Japan.
authors: Atsuko
authors: A
authors: Watarai
authors: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute Aichi 480-1195, Japan.
authors: Masaki
authors: M
authors: Kondo
authors: Laboratory of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya 464-0037, Japan.
authors: Koichi
authors: K
authors: Kato
authors: Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute Aichi 480-1195, Japan.
authors: Jiro
authors: J
authors: Nakamura
authors: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors: Takashi
authors: T
authors: Yokochi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000077405:Irbesartan; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D013777:Tetrazoles; C482199:lipopolysaccharide, E coli O55-B5; D009569:Nitric Oxide; D016899:Interferon-beta; D000077405:Irbesartan
keywords: High-mobility group box 1; Interferon-β; Irbesartan; Lipopolysaccharide; Nitric oxide