IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro
| العنوان: | IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro |
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| المؤلفون: | Géraldine Bart, Benoit Le Goff, Pierre Layrolle, Cem Gabay, Frédéric Blanchard, Gaby Palmer, Aurélie Najm, Régis Brion, S Touchais, Valérie Trichet, Marie-Astrid Boutet |
| المساهمون: | Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe Labellisée LIGUE 2012 [Nantes], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Pathology and Immunology [Geneva, Switzerland] (Clinical Pathology Division), University of Geneva [Switzerland]-Geneva University Hospitals - HUG [Switzerland], Division of Rheumatology [Geneva, Switzerland], Geneva University Hospital, Geneva-Department of Internal Medicine [Genève], This work was supported by Inserm and in part by the Arthritis Foundation and by the French Society of Rheumatology. M-AB was a recipient from a fellowship from the French Ministry of Research. CG is supported by grants from the Swiss National Science Foundation (310030_152638), the Rheumasearch Foundation, the Uniscientia Foundation and the Institute of Arthritis Research., maurice, sandrine, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université de Genève = University of Geneva (UNIGE)-Geneva University Hospitals - HUG [Switzerland] |
| المصدر: | Annals of the Rheumatic Diseases, Vol. 76, No 7 (2017) pp. 1304-1312 Annals of the Rheumatic Diseases Annals of the Rheumatic Diseases, BMJ Publishing Group, 2017, 76 (7), pp.1304-1312. ⟨10.1136/annrheumdis-2016-210630⟩ |
| بيانات النشر: | BMJ, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Cartilage, Articular, 0301 basic medicine, medicine.medical_treatment, Arthritis, Macrophages/immunology, Interleukin-23, Arthritis, Rheumatoid, Mice, 0302 clinical medicine, Tumor Necrosis Factor-alpha/genetics/immunology, Immunology and Allergy, ddc:616, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Interleukin-17, Synovial Membrane, Interleukin, Arthritis, Experimental/genetics/immunology, Immunohistochemistry, Interleukin-17/genetics/immunology, 3. Good health, Synovial Membrane/cytology, medicine.anatomical_structure, Cytokine, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Cytokines, Tumor necrosis factor alpha, Arthritis, Rheumatoid/immunology, Blotting, Western, Immunology, Enzyme-Linked Immunosorbent Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, In Vitro Techniques, Real-Time Polymerase Chain Reaction, Bone and Bones, Interleukin-6/genetics/immunology, General Biochemistry, Genetics and Molecular Biology, Cell Line, Proinflammatory cytokine, 03 medical and health sciences, Rheumatology, Fibroblasts/immunology, medicine, Animals, Humans, Th17 Cells/immunology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Inflammation, Interleukin-6, Tumor Necrosis Factor-alpha, business.industry, Interleukins, Macrophages, Cartilage, Bone and Bones/diagnostic imaging, X-Ray Microtomography, Fibroblasts, Interleukins/genetics/immunology, medicine.disease, Arthritis, Experimental, Cartilage, Articular/diagnostic imaging, 030104 developmental biology, Interleukin-23/genetics/immunology, Cell culture, Culture Media, Conditioned, Th17 Cells, Transcriptome, business |
| الوصف: | International audience; OBJECTIVES:Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro.METHODS:Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, immunohistochemistry, microCT, Luminex and RT-qPCR analysis. THP-1 macrophages were transduced with a lentiviral vector to overexpress IL-38.RESULTS:Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 cytokines (IL-17, IL-23, IL-22) and TNFα. However, IL-38 overexpression had no effect on cartilage or bone destruction. In vitro, the THP-1 monocytic cell line expressed less IL-6, TNFα and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, also exert an anti-inflammatory effect on human primary macrophages and synovial fibroblasts from patients with RA.CONCLUSIONS:This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis. IL-38 may exert its anti-inflammatory effects by decreasing the production of proinflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis. |
| وصف الملف: | application/pdf |
| تدمد: | 1468-2060 0003-4967 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a12249ab5b298f5554c2d6ef3910cfe6Test https://doi.org/10.1136/annrheumdis-2016-210630Test |
| حقوق: | EMBARGO |
| رقم الانضمام: | edsair.doi.dedup.....a12249ab5b298f5554c2d6ef3910cfe6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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