Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice

Skeletal Muscle
Eiji WadaRyoichi Matsuda

Abstract

Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles. As mdx mice and DMD patients, we found that IL-6 levels in the skeletal muscle were significantly increased in dKO mice. Thus, in this study, we aimed to analyze the effects of IL-6 receptor (IL-6R) blockade on the muscle pathology of dKO mice. Male dKO mice were administered an initial injection (200 mg/kg intraperitoneally (i.p.)) of either the anti-IL-6R antibody MR16-1 or an isotype-matched control rat IgG at the age of 14 days, and were then given weekly injections (25 mg/kg i.p.) until 90 days of age. Treatment of dKO mice with the MR16-1 antibody successfully inhibited the IL-6 pathway in the skeletal muscle and resulted in a significant reduction in the expression levels of phosphorylated signal transducer and a...Continue Reading

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Citations

Aug 4, 2018·International Journal of Molecular Sciences·Eleonora GuadagninYi-Wen Chen
Sep 19, 2018·Current Osteoporosis Reports·Antoine Boulanger PietteJérôme Frenette
Jan 28, 2018·Current Rheumatology Reports·Marissa J SchaferNathan K LeBrasseur
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Nov 8, 2020·International Journal of Molecular Sciences·Anna JaśkiewiczBeata Pająk
Dec 19, 2020·Genomics, Proteomics & Bioinformatics·Monika HillerPietro Spitali
Mar 19, 2021·Frontiers in Endocrinology·Sonja BuvinicViviana Toro-Ibacache
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Jul 6, 2021·Therapeutic Advances in Musculoskeletal Disease·Jean-Guillaume LetarouillyJulien Paccou
Jul 3, 2021·International Journal of Molecular Sciences·Byongsun LeeJaekyung Shim

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Methods Mentioned

BETA
protein assay
ELISA
PCR

Software Mentioned

IN Cell Developer Toolbox
SPSS
NIH ImageJ

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