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http://purl.uniprot.org/citations/19109961http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19109961http://www.w3.org/2000/01/rdf-schema#comment"

Background and aims

Tumor necrosis factor (TNF) superfamily members have attracted attention as new therapeutic targets for treating inflammatory disease. TNF-like weak inducer of apoptosis (TWEAK) is a unique, multifunctional TNF family cytokine that signals through its receptor, fibroblast growth factor-inducible molecule 14 (Fn14). The role of this pathway in the intestine has not been previously reported.

Methods

The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model was conducted in TWEAK- or Fn14-deficient mice or in normal mice treated with a TWEAK-blocking monoclonal antibody, and clinical severity, histopathology, immunohistochemistry for cell infiltrates, TWEAK and Fn14, gene expression profiling in the colon, and systemic adaptive immunity were assessed. The effect of TWEAK on colon epithelial cell production of inflammatory mediators was analyzed in vitro. The gamma-irradiation injury model was conducted in TWEAK- or Fn14-deficient mice, and crypt epithelial death was assessed.

Results

Colitis severity and histologic scores were significantly reduced by TWEAK pathway deficiency or TWEAK-blocking monoclonal antibody. Neutrophil and macrophage infiltrates, chemokines, cytokines, and matrix metalloproteinase expression were reduced in the TWEAK-deficient colon after TNBS administration; however, systemic adaptive immune responses to trinitrophenyl were not altered. Fn14 is expressed on colon epithelial cells in TNBS colitis, and TWEAK induces epithelial production of pathogenic mediators. TWEAK also regulates intestinal epithelial turnover, as evidenced by reduced epithelial cell death after gamma-irradiation injury in TWEAK and Fn14 knockout mice.

Conclusions

Our studies elucidate a nonredundant TWEAK-intestinal epithelial cell axis and suggest that blocking TWEAK may dampen chronic intestinal inflammation and allow normal epithelial repair."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2008.11.017"xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Dong X."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Scott M.L."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Wu P."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Borodovsky A."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Shearstone J.R."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Michaelson J.S."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Runkel L."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Dohi T."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Burkly L.C."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Jakubowski A."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Kawashima R."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/author"Rajman L."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/name"Gastroenterology"xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/pages"912-923"xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/title"TWEAK/Fn14 pathway: a nonredundant role in intestinal damage in mice through a TWEAK/intestinal epithelial cell axis."xsd:string
http://purl.uniprot.org/citations/19109961http://purl.uniprot.org/core/volume"136"xsd:string
http://purl.uniprot.org/citations/19109961http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19109961
http://purl.uniprot.org/citations/19109961http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19109961
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http://purl.uniprot.org/uniprot/#_A0A3B2W475-mappedCitation-19109961http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19109961
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