Inflammasome up-regulation and activation in dysferlin-deficient skeletal muscle

dc.creatorRawat, Rashmi
dc.creatorCohen, Tatiana V.
dc.creatorAmpong, Beryl
dc.creatorFrancia, Dwight
dc.creatorPons, Andrea Henriques
dc.creatorHoffman, Eric P.
dc.creatorNagaraju, Kanneboyina
dc.date2018-05-03T17:33:30Z
dc.date2018-05-03T17:33:30Z
dc.date2010
dc.date.accessioned2023-09-26T21:04:48Z
dc.date.available2023-09-26T21:04:48Z
dc.identifierRAWAT, Rashmi; et al. Inflammasome Up-Regulation and Activation in Dysferlin-Deficient Skeletal Muscle. The American Journal of Pathology, v.176, n.6, p.2891-2990, June 2010.
dc.identifier0002-9440
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/26253
dc.identifier10.2353/ajpath.2010.090058
dc.identifier1525-2191
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8868808
dc.descriptionA deficiency of the dysferlin protein results in limb girdle muscular dystrophy type 2B and Miyoshi myopathy, with resulting plasma membrane abnormalities in myofibers. Many patients show muscle inflammation, but the molecular mechanisms that initiate and perpetuate this inflammation are not well understood. We previously showed abnormal activation of macrophages and hypothesized that activation of the inflammasome pathway may play a role in disease progression. To test this, we studied the inflammasome molecular platform in dysferlin-deficient human and mouse muscle. Consistent with our model, components of the NACHT, LRR and PYD-containing proteins (NALP)-3 inflammasome pathway were specifically up-regulated and activated in dysferlin-deficient but not in dystrophin-deficient and normal muscle. We demonstrate for the first time that normal primary skeletal muscle cells are capable of secreting IL-1beta in response to combined treatment with lipopolysaccharide and the P2X7 receptor agonist, benzylated ATP, suggesting that not only immune cells but also muscle cells can actively participate in inflammasome formation. In addition, we show that dysferlin-deficient primary muscle cells express toll-like receptors (TLRs; TLR-2 and TLR-4) and can efficiently produce IL-1beta in response to lipopolysaccharide and benzylated ATP. These data indicate that skeletal muscle is an active contributor of IL-1beta and strategies that interfere with this pathway may be therapeutically useful for patients with limb girdle muscular dystrophy type 2B.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Investigative Pathology
dc.rightsrestricted access
dc.subjectInflamassomos
dc.subjectMúsculo esquelético
dc.subjectDisferina
dc.subjectRegulação para Cima
dc.subjectInflammasome
dc.subjectdysferlin
dc.subjectskeletal muscle
dc.subjectUp-Regulation
dc.titleInflammasome up-regulation and activation in dysferlin-deficient skeletal muscle
dc.typeArticle


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