title: Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages.
abstract: State of the art. Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation and osteophyte formation. OA physiopathology is multifactorial and involves mechanical and hereditary factors. So far, there is neither preventive medicine to delay cartilage breakdown nor curative treatment. Objectives. To investigate pro-inflammatory paracrine interactions between human primary chondrocytes and macrophages following interleukin-1-β (IL-1β) treatment; to evaluate the molecular mechanism responsible for the inhibitory effect of resveratrol. Results. The activation of NF-κB in chondrocytes by IL-1β induced IL-6 secretion. The latter will then activate STAT3 protein in macrophages. Moreover, STAT3 was able to positively regulate IL-6 secretion, as confirmed by the doubling level of IL-6 in the coculture compared to macrophage monoculture. These experiments confirm the usefulness of the coculture model in the inflammatory arthritis-linked process as a closer biological situation to the synovial joint than separated chondrocytes and macrophages. Il also demonstrated the presence of an inflammatory amplification loop induced by IL-1β. Resveratrol showed a strong inhibitory effect on the pro-inflammatory marker secretion. The decrease of IL-6 secretion is dependent on the NFκB inhibition in the chondrocytes. Such reduction of the IL-6 level can limit STAT3 activation in the macrophages, leading to the interruption of the inflammatory amplification loop. Conclusion. These results increase our understanding of the anti-inflammatory actions of resveratrol and open new potential approaches to prevent and treat osteoarthritis.
authors.affiliation: Laboratoire de Lipides, Nutrition, Cancer, Université de Bourgogne-Franche Comté, Dijon F21000, France. limagne.emeric@yahoo.fr.|Laboratoire de Biochimie du Peroxysome, Inflammation et Métabolisme des Lipides (BioPeroxIL EA 7270), Faculté des Sciences Gabriel, Dijon F21000, France. limagne.emeric@yahoo.fr.|"Chemotherapy, Lipid Metabolism and Antitumoral Immune Response" Team, Faculty of Health Sciences, INSERM (Institut National de la Santé et de la recherché Médicale) Research Center U866, Dijon F21000, France. limagne.emeric@yahoo.fr.
authors.forename: Emeric
authors.initials: E
authors.lastname: Limagne
authors.affiliation: Laboratoire de Lipides, Nutrition, Cancer, Université de Bourgogne-Franche Comté, Dijon F21000, France. allan.lancon@gmail.com.|Laboratoire de Biochimie du Peroxysome, Inflammation et Métabolisme des Lipides (BioPeroxIL EA 7270), Faculté des Sciences Gabriel, Dijon F21000, France. allan.lancon@gmail.com.
authors.forename: Allan
authors.initials: A
authors.lastname: Lançon
authors.affiliation: Laboratoire de Lipides, Nutrition, Cancer, Université de Bourgogne-Franche Comté, Dijon F21000, France. dominique.delmas@u-bourgogne.fr.|"Chemotherapy, Lipid Metabolism and Antitumoral Immune Response" Team, Faculty of Health Sciences, INSERM (Institut National de la Santé et de la recherché Médicale) Research Center U866, Dijon F21000, France. dominique.delmas@u-bourgogne.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Delmas
authors.affiliation: Laboratoire de Lipides, Nutrition, Cancer, Université de Bourgogne-Franche Comté, Dijon F21000, France. malki@u-bourgogne.fr.|Laboratoire de Biochimie du Peroxysome, Inflammation et Métabolisme des Lipides (BioPeroxIL EA 7270), Faculté des Sciences Gabriel, Dijon F21000, France. malki@u-bourgogne.fr.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Cherkaoui-Malki
authors.affiliation: Laboratoire de Lipides, Nutrition, Cancer, Université de Bourgogne-Franche Comté, Dijon F21000, France. Norbert.Latruffe@u-bourgogne.fr.|Laboratoire de Biochimie du Peroxysome, Inflammation et Métabolisme des Lipides (BioPeroxIL EA 7270), Faculté des Sciences Gabriel, Dijon F21000, France. Norbert.Latruffe@u-bourgogne.fr.
authors.forename: Norbert
authors.initials: N
authors.lastname: Latruffe
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D018920:Coculture Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D053583:Interleukin-1beta; D013267:Stilbenes; D000077185:Resveratrol
keywords: IL1-β; NF-κB; STAT3; chondrocyte; macrophage; resveratrol