Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents macrophage activation.
We investigated the effect of hydroxytyrosol (HT), a phenolic compound from virgin olive oil, on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in J774 murine macrophages stimulated with lipopolysaccharide (LPS). Incubation of cells with LPS caused an increase in iNOS and COX-2 mRNA and protein level as well as ROS generation, which was prevented by HT. In addition, HT blocked the activation of nuclear factor-kappaB (NF-kappaB), signal transducer and activator of transcription-1alpha (STAT-1alpha) and interferon regulatory factor-1 (IRF-1). These results, showing that HT down-regulates iNOS and COX-2 gene expression by preventing NF-kappaB, STAT-1alpha and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes.
Maiuri
Maria Chiara
MC
Dipartimento di Farmacologia Sperimentale, Università degli Studi di Napoli Federico II, Via D. Montesano n. 49, 80131 Naples, Italy.
De Stefano
Daniela
D
Di Meglio
Paola
P
Irace
Carlo
C
Savarese
Maria
M
Sacchi
Raffaele
R
Cinelli
Maria Pia
MP
Carnuccio
Rosa
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D000069463:Olive Oil; D010938:Plant Oils; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C079868:gamma interferon activation factor; C005975:3,4-dihydroxyphenylethanol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D010626:Phenylethyl Alcohol