TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis.
Sokulsky, LA
Collison, AM
Nightingale, S
Fevre, AL
Percival, E
Starkey, MR
Hansbro, PM
Foster, PS
Mattes, J
- Publisher:
- AMER PHYSIOLOGICAL SOC
- Publication Type:
- Journal Article
- Citation:
- American journal of physiology. Gastrointestinal and liver physiology, 2016, 311, (6), pp. G998-G1008
- Issue Date:
- 2016-12
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TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis.pdf | Published version | 1.49 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Sokulsky, LA | |
dc.contributor.author | Collison, AM | |
dc.contributor.author | Nightingale, S | |
dc.contributor.author | Fevre, AL | |
dc.contributor.author | Percival, E | |
dc.contributor.author | Starkey, MR | |
dc.contributor.author | Hansbro, PM | |
dc.contributor.author | Foster, PS | |
dc.contributor.author | Mattes, J | |
dc.date.accessioned | 2020-12-23T00:40:54Z | |
dc.date.available | 2016-10-05 | |
dc.date.available | 2020-12-23T00:40:54Z | |
dc.date.issued | 2016-12 | |
dc.identifier.citation | American journal of physiology. Gastrointestinal and liver physiology, 2016, 311, (6), pp. G998-G1008 | |
dc.identifier.issn | 0193-1857 | |
dc.identifier.issn | 1522-1547 | |
dc.identifier.uri | http://hdl.handle.net/10453/144936 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | AMER PHYSIOLOGICAL SOC | |
dc.relation.ispartof | American journal of physiology. Gastrointestinal and liver physiology | |
dc.relation.isbasedon | 10.1152/ajpgi.00151.2016 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 0606 Physiology, 1116 Medical Physiology | |
dc.subject.classification | Gastroenterology & Hepatology | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice, Inbred BALB C | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Egg Hypersensitivity | |
dc.subject.mesh | Fibrosis | |
dc.subject.mesh | Dexamethasone | |
dc.subject.mesh | Microtubule Proteins | |
dc.subject.mesh | Ovalbumin | |
dc.subject.mesh | Interleukin-3 | |
dc.subject.mesh | Nuclear Proteins | |
dc.subject.mesh | Transcription Factors | |
dc.subject.mesh | Bronchodilator Agents | |
dc.subject.mesh | Anti-Inflammatory Agents | |
dc.subject.mesh | Interleukin-5 | |
dc.subject.mesh | Cytokines | |
dc.subject.mesh | Case-Control Studies | |
dc.subject.mesh | Child | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | TNF-Related Apoptosis-Inducing Ligand | |
dc.subject.mesh | Chemokine CCL11 | |
dc.subject.mesh | Protein Phosphatase 2 | |
dc.subject.mesh | Eosinophilic Esophagitis | |
dc.subject.mesh | Salmeterol Xinafoate | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Anti-Inflammatory Agents | |
dc.subject.mesh | Bronchodilator Agents | |
dc.subject.mesh | Case-Control Studies | |
dc.subject.mesh | Chemokine CCL11 | |
dc.subject.mesh | Child | |
dc.subject.mesh | Cytokines | |
dc.subject.mesh | Dexamethasone | |
dc.subject.mesh | Egg Hypersensitivity | |
dc.subject.mesh | Eosinophilic Esophagitis | |
dc.subject.mesh | Female | |
dc.subject.mesh | Fibrosis | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Interleukin-3 | |
dc.subject.mesh | Interleukin-5 | |
dc.subject.mesh | Male | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Inbred BALB C | |
dc.subject.mesh | Microtubule Proteins | |
dc.subject.mesh | Nuclear Proteins | |
dc.subject.mesh | Ovalbumin | |
dc.subject.mesh | Protein Phosphatase 2 | |
dc.subject.mesh | Salmeterol Xinafoate | |
dc.subject.mesh | TNF-Related Apoptosis-Inducing Ligand | |
dc.subject.mesh | Transcription Factors | |
dc.title | TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis. | |
dc.type | Journal Article | |
utslib.citation.volume | 311 | |
utslib.location.activity | United States | |
utslib.for | 0606 Physiology | |
utslib.for | 1116 Medical Physiology | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
utslib.copyright.status | closed_access | * |
dc.date.updated | 2020-12-23T00:40:38Z | |
pubs.issue | 6 | |
pubs.publication-status | Published | |
pubs.volume | 311 | |
utslib.citation.issue | 6 |
Abstract:
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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