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TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis.
Sokulsky, Leon A; Collison, Adam M; Nightingale, Scott; Fevre, Anna Le; Percival, Elizabeth; Starkey, Malcolm R; Hansbro, Philip M; Foster, Paul S; Mattes, Joerg.
Afiliação
  • Sokulsky LA; The Priority Research Centre GrowUpWell, Newcastle, Australia.
  • Collison AM; The Priority Research Centre GrowUpWell, Newcastle, Australia; Adam.Collison@newcastle.edu.au.
  • Nightingale S; The Priority Research Centre GrowUpWell, Newcastle, Australia.
  • Fevre AL; The Priority Research Centre GrowUpWell, Newcastle, Australia.
  • Percival E; The Priority Research Centre GrowUpWell, Newcastle, Australia.
  • Starkey MR; Department of Gastroenterology and the Department of Respiratory and Sleep Medicine, John Hunter Children's Hospital, Newcastle, Newcastle, Australia.
  • Hansbro PM; The Priority Research Centre GrowUpWell, Newcastle, Australia.
  • Foster PS; Priority Research Centre for Lung Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia; and.
  • Mattes J; Priority Research Centre for Lung Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia; and.
Am J Physiol Gastrointest Liver Physiol ; 311(6): G998-G1008, 2016 12 01.
Article em En | MEDLINE | ID: mdl-27742702
Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNF-related apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through the upregulation of the E3 ubiquitin ligase Midline (MID)-1 and subsequent downregulation of protein phosphatase 2A (PP2A), but the role of this pathway in EoE that is experimentally induced by repeated food antigen challenges has not been investigated. Esophageal mucosal biopsies were collected from children with EoE and controls and assessed for TRAIL and MID-1 protein and mRNA transcript levels. Wild-type and TRAIL-deficient (Tnfsf10-/-) mice were administered subcutaneous ovalbumin (OVA) followed by oral OVA challenges. In separate experiments, OVA-challenged mice were intraperitoneally administered salmeterol or dexamethasone. Esophageal biopsies from children with EoE revealed increased levels of TRAIL and MID-1 and reduced PP2A activation compared with controls. Tnfsf10-/- mice were largely protected from esophageal fibrosis, eosinophilic inflammation, and the upregulation of TSLP, IL-5, IL-13, and CCL11 when compared with wild-type mice. Salmeterol administration to wild-type mice with experimental EoE restored PP2A activity and also prevented esophageal eosinophilia, inflammatory cytokine expression, and remodeling, which was comparable to the treatment effect of dexamethasone. TRAIL and PP2A regulate inflammation and fibrosis in experimental EoE, which can be therapeutically modulated by salmeterol.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Broncodilatadores / Hipersensibilidade a Ovo / Ligante Indutor de Apoptose Relacionado a TNF / Proteína Fosfatase 2 / Esofagite Eosinofílica / Xinafoato de Salmeterol Idioma: En Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Broncodilatadores / Hipersensibilidade a Ovo / Ligante Indutor de Apoptose Relacionado a TNF / Proteína Fosfatase 2 / Esofagite Eosinofílica / Xinafoato de Salmeterol Idioma: En Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Austrália