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IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-01671438
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Submitted on : Friday, December 22, 2017 - 11:40:43 AM
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Marie-Astrid Boutet, Aurelie Najm, Géraldine Bart, Régis Brion, Sophie Touchais, et al.. IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro.. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2017, 76 (7), pp.1304-1312. ⟨10.1136/annrheumdis-2016-210630⟩. ⟨inserm-01671438⟩

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