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Several myopathies are characterized by the presence of a chronic inflammation that aggravates the disease. Such inflammation arises from a major production of pro-inflammatory cytokines, in particular TNFα and IL-Iβ. Adiponectin (ApN) is a hormone abundantly secreted by adipocytes under standard conditions. It exerts pleiotropic effects including as an insulin sensitizer, fat burner and anti-inflammatory. It has been shown in the laboratory that ApN stimulates the expression of mir-711. This micro-RNA helps to reduce inflammation through the downregulation of genes coding for proteins involved in the activation of the pro-inflammatory transcription factor NF-kB. MIR-711 also downregulates the expression of genes coding for proteins located upstream of the NLRP3 inflammasome complex, which is essential to cleave and thereby activate IL-Iβ in a variety of cell types. However, the presence and the role of the NLRP complex in skeletal muscle have not been investigated until now. The aim of this work is to study the expression and regulation of the NLRP3 complex in the skeletal muscle as well as its role in muscle inflammation. First, we showed the presence of NLRP3 in the muscle fibers. Second, we showed that treatment which ApN or miR-711 reduced the LPS-induced expression of NLRP3 in C2C12 cells. Conversely, inhibition of miR-711 abrogated the anti-inflammatory action of ApN on NLRP3, suggesting that ApN inhibits NLRP3 through miR-711. All of these data were also confirmed in vivo. Moreover, we showed that, in mdx mice, the expression of NLRP3 is strongly increased compared to the control mice whereas the overexpression of the ApN reduced NLRP3 in mdx mice. Finally, we showed that mdx mice deficient for NLRP3 have improved physical performance as well as reduced inflammation, oxidative stress and decrease muscle damage when compared to regular mdx mice. In conclusion, these data highlights a deleterious inflammatory role of the NLRP3 inflammasome complex in the progression of DMD while specifying the underlying mechanisms of the anti-inflammatory action of ApN and miR-711 thus opening new therapeutic perspectives to control muscle inflammation. De nombreuses myopathies se caractérisent par la présence d'une inflammation chronique qui joue un rôle aggravant dans la maladie. Cette inflammation résulte d'une sécrétion importante de différentes cytokines pro-inflammatoires, notamment du TNFa et de l'IL-1. L'adiponectine (ApN) est une hormone abondamment sécrétée par les adipocytes en condition normale. Elle exerce des effets pléiotropes notamment en tant que sensibilisateur à l'insuline, brûleur de graisse et anti-inflammatoire. Il a été montré au laboratoire que l'ApN était capable d'inhiber l'inflammation au niveau du muscle squelettique et ainsi d'améliorer les performances physiques de souris mdx, un modèle murin de la myopathie de Duchenne. Par ailleurs, il a récemment été démontré que l'ApN stimule l'expression du miR-711. Ce microARN contribue à diminuer l'inflammation via la répression de gènes codant pour des protéines impliquées dans l’activation du facteur de transcription pro-inflammatoire NF-KB. Le miR-711 inhibe également l'expression de gènes codant pour des protéines situées en amont de l'activation du complexe NLRP3 inflammasome qui s'avère essentiel dans différents types cellulaires pour cliver et ainsi activer la forme précurseur d'IL-1. Or, la présence et le rôle du complexe NLRP3 dans le muscle squelettique n'ont jusqu'alors pas été investigués. L'objectif de ce travail est donc d'étudier l'expression de NLRP3 dans le muscle squelettique, d'étudier sa régulation ainsi que son rôle dans l'inflammation du muscle squelettique. Dans un premier temps, nous avons montré la présence de NLRP3 dans les fibres musculaires. Dans un deuxième temps, nous avons montré qu'un traitement à l'ApN ou au miR-711 réduit l'expression, induite par le LPS, de NLRP3 dans les cellules C2Cl 2. A l'inverse, l'inhibition du miR-711 réduit l'action anti-inflammatoire de l'ApN sur NLRP3 suggérant que l'ApN inhibe NLRP3 via le miR-711. Ces données ont ensuite été confirmées in vivo. De plus, nous avons montré chez les souris mdx que l'expression de NLRP3 est fortement augmentée par rapport aux souris contrôles tandis que la surexpression de l'ApN chez des souris mdx induit une diminution de NLRP3. Dans un troisième temps, nous avons montré que des souris mdx déficientes pour NLRP3 présentent des performances physiques améliorées ainsi qu'une inflammation, un stress oxydatif et des dommages musculaires diminués par rapport aux souris mdx. En conclusion, ces données permettent de mettre en évidence un rôle inflammatoire délétère du complexe NLRP3 inflammasome dans l'évolution de la myopathie de Duchenne tout en précisant les mécanismes sous-jacents des propriétés bénéfiques anti-inflammatoires de l 'ApN et du miR-711, ouvrant ainsi de nouvelles perspectives thérapeutiques pour contrôler l'inflammation musculaire.

Inflammasomes --- NLR Family, Pyrin Domain-Containing 3 Protein --- Mice --- Muscular Dystrophy, Duchenne

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Interleukin-1 --- Interleukin-1 receptor antagonist --- anti-interleukin-1 monoclonal antibody --- Inflammasomes --- Chronic inflammatory diseases --- Autoinflammatory diseases --- Arthritis --- Osteoathritis --- Skin Diseases --- crystal-induced inflammation

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Interferon --- Cytokines --- Interférons --- Periodicals --- Périodiques --- Inflammation --- Interferons. --- Cytokines. --- Inflammation Mediators. --- Interferon. --- Mediators --- Mediators. --- Interferons --- Inflammatory mediators --- Mediators of inflammation --- Mediators of Inflammation --- Mediators, Inflammation --- Inflammatory process --- Antineoplastic agents --- Antiviral agents --- Glycoproteins --- Lymphokines --- Biomolecules --- Cellular immunity --- Immune response --- Inflammasomes --- Viral Interference --- Pathology --- Anti-inflammatory agents --- Regulation --- interferon --- Microbiology & Immunology --- Cytokine --- Interferó. --- Citocines. --- Inflammation Mediators --- Inflammation (Pathologie) --- Médiateurs

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"The Innate Immune Response to Noninfectious Stressors: Human and Animal Models highlights fundamental mechanisms of stress response and important findings on how the immune system is affected, and in turn affects such a response. In addition, this book covers the crucial link between stress response and energy metabolism, prompts a re-appraisal of some crucial issues, and helps to define research priorities in this fascinating, somehow elusive field of investigation."--

Natural immunity --- Immune response. --- Immunity, Innate. --- Bacterial Infections --- Homeostasis --- Effect of stress on. --- immunology. --- Innate Immune Response --- Innate Immunity --- Immunity, Native --- Immunity, Natural --- Immunity, Non-Specific --- Resistance, Natural --- Immune Response, Innate --- Immune Responses, Innate --- Immunity, Non Specific --- Innate Immune Responses --- Native Immunity --- Natural Immunity --- Natural Resistance --- Non-Specific Immunity --- Inflammation --- Receptors, Pattern Recognition --- Adaptive Immunity --- Inflammasomes --- Immunology --- Stress (Physiology)

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Endotoxins --- Endotoxins. --- Immunity, Innate. --- Innate Immune Response --- Innate Immunity --- Immunity, Native --- Immunity, Natural --- Immunity, Non-Specific --- Resistance, Natural --- Immune Response, Innate --- Immune Responses, Innate --- Immunity, Non Specific --- Innate Immune Responses --- Native Immunity --- Natural Immunity --- Natural Resistance --- Non-Specific Immunity --- Bacterial pyrogens --- Endotoxin --- Lipopolysaccharides, Microbial --- Microbial lipopolysaccharides --- Receptors, Pattern Recognition --- Adaptive Immunity --- Inflammasomes --- Pyrogens --- Bacterial cell walls --- Bacterial toxins --- Gram-negative bacteria --- Microbial lipids --- Microbial polysaccharides --- Inflammation