title: The molecular events behind ferulic acid mediated modulation of IL-6 expression in LPS-activated Raw 264.7 cells.
abstract: Identification of new antioxidant and anti-inflammatory bioactive molecules is an important tool for selecting effective formulations for the treatment of inflammation. The mouse macrophage cell line RAW 264.7, lipopolysaccharide (LPS)-activated, is associated with an inflammation response. Activated macrophages produce reactive oxygen species (ROS), nitric oxide (NO) and inflammatory cytokines such as IL-6, TNF-α and IL-10. In the present study we have showed that pre-treatment with Ferulic Acid (FA) reduces NO accumulation in the culture medium of LPS-induced macrophage cells. Moreover, real-time experiments have revealed that FA has an inhibitory effect at the transcriptional level on the expression of some inflammatory mediators such as IL-6, TNF-α and iNOS and an activation effect on the expression of some antioxidant molecules such as Metallothioneins (MT-1, MT-2). Importantly, we have found that FA reduced the translocation of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor-κB (NF-κB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibited IL-6 and NF-κB promoter activity in a luciferase assay. Our data clearly suggest that FA anti-inflammatory effects are mainly mediated through IKK/NF-κB signalling pathway. Therefore, FA could represent a new natural drug extremely useful to improve anti-inflammatory treatment.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146 Palermo, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Lampiasi
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146 Palermo, Italy. Electronic address: montana@ibim.cnr.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Montana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003373:Coumaric Acids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C004999:ferulic acid; D051550:I-kappa B Kinase
keywords: Ferulic Acid; IL-6; LPS; Metallothioneins; NF-κB; NO; Nrf2; ROS; iNOS