PMID- 26612455 OWN - NLM STAT- MEDLINE DCOM- 20161020 LR - 20161230 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 221 IP - 3 DP - 2016 Mar TI - The molecular events behind ferulic acid mediated modulation of IL-6 expression in LPS-activated Raw 264.7 cells. PG - 486-93 LID - S0171-2985(15)30085-1 [pii] LID - 10.1016/j.imbio.2015.11.001 [doi] AB - 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-alpha 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-alpha 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-kappaB (NF-kappaB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibited IL-6 and NF-kappaB promoter activity in a luciferase assay. Our data clearly suggest that FA anti-inflammatory effects are mainly mediated through IKK/NF-kappaB signalling pathway. Therefore, FA could represent a new natural drug extremely useful to improve anti-inflammatory treatment. CI - Copyright (c) 2015 Elsevier GmbH. All rights reserved. FAU - Lampiasi, Nadia AU - Lampiasi N AD - Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146 Palermo, Italy. FAU - Montana, Giovanna AU - Montana G AD - 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. LA - eng PT - Journal Article DEP - 20151110 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Antioxidants) RN - 0 (Coumaric Acids) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 31C4KY9ESH (Nitric Oxide) RN - AVM951ZWST (ferulic acid) RN - EC 2.7.11.10 (I-kappa B Kinase) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Cell Line MH - Coumaric Acids/*pharmacology MH - Gene Expression MH - Gene Expression Regulation/*drug effects MH - Genes, Reporter MH - I-kappa B Kinase/metabolism MH - Inflammation/genetics/immunology/metabolism MH - Interleukin-6/*genetics/*metabolism MH - Lipopolysaccharides/immunology MH - Macrophage Activation/*drug effects/*immunology MH - Macrophages/*drug effects/immunology/*metabolism MH - Mice MH - Models, Molecular MH - NF-kappa B/metabolism MH - Nitric Oxide/metabolism MH - Protein Transport MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Ferulic Acid OT - IL-6 OT - LPS OT - Metallothioneins OT - NF-kappaB OT - NO OT - Nrf2 OT - ROS OT - iNOS EDAT- 2015/11/28 06:00 MHDA- 2016/10/21 06:00 CRDT- 2015/11/28 06:00 PHST- 2015/09/24 00:00 [received] PHST- 2015/10/30 00:00 [revised] PHST- 2015/11/02 00:00 [accepted] PHST- 2015/11/28 06:00 [entrez] PHST- 2015/11/28 06:00 [pubmed] PHST- 2016/10/21 06:00 [medline] AID - S0171-2985(15)30085-1 [pii] AID - 10.1016/j.imbio.2015.11.001 [doi] PST - ppublish SO - Immunobiology. 2016 Mar;221(3):486-93. doi: 10.1016/j.imbio.2015.11.001. Epub 2015 Nov 10.