title: Influence of olive-derived hydroxytyrosol on the toll-like receptor 4-dependent inflammatory response of mouse peritoneal macrophages.
abstract: Macrophages play important roles in the host innate immune response and are involved in the onset of diseases caused by inflammation. Toll-like receptor 4 (TLR4)-mediated inflammatory responses of macrophages may be associated with diseases such as diabetes and diseases of the cardiovascular system. Hydroxytyrosol (HT) exerts strong antioxidant and anti-inflammatory effects and may be applied in the treatment of inflammatory diseases. In the present study conducted in vitro, we investigated the effects of the TLR4-dependent anti-inflammatory effect of HT on peritoneal macrophage of BALB/c mice. We show here that the elevated levels of iNOS gene expression and nitric oxide production induced by lipopolysaccharide (LPS) (0.25 μg/ml) were suppressed by HT (12.5 μg/ml). LPS-dependent NF-κB gene expression and phosphorylation of NF-κB were not affected by HT under these conditions. In contrast, the expression of TNF-α was significantly increased in the presence of LPS and HT. These results suggest that HT suppressed nitric oxide production by decreasing iNOS gene expression through a mechanism independent of the NF-κB signaling pathway. These novel findings suggest that the modulation by HT of the expression of genes involved in inflammation may involve multiple mechanisms.
authors.affiliation: Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Vuong N
authors.initials: VN
authors.lastname: Bui
authors.affiliation: Department of Transplant Immunology, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Department of Transplant Immunology, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan; Department of Surgery II, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan. Electronic address: hogawa@obihiro.ac.jp.
authors.forename: Haruko
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Imai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D031658:Olea / Q000737:chemistry*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000276:immunology / Q000302:isolation & purification; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; C005975:3,4-dihydroxyphenylethanol; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010626:Phenylethyl Alcohol
keywords: Hydroxytyrosol; Inflammation; Lipopolysaccharide; Macrophage; Toll-like receptor 4