Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/20875417http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20875417http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

Premature neonates are predisposed to necrotizing enterocolitis (NEC), an idiopathic, inflammatory bowel necrosis. We investigated whether NEC occurs in the preterm intestine due to incomplete noninflammatory differentiation of intestinal macrophages, which increases the risk of a severe mucosal inflammatory response to bacterial products.

Methods

We compared inflammatory properties of human/murine fetal, neonatal, and adult intestinal macrophages. To investigate gut-specific macrophage differentiation, we next treated monocyte-derived macrophages with conditioned media from explanted human fetal and adult intestinal tissues. Transforming growth factor-β (TGF-β) expression and bioactivity were measured in fetal/adult intestine and in NEC. Finally, we used wild-type and transgenic mice to investigate the effects of deficient TGF-β signaling on NEC-like inflammatory mucosal injury.

Results

Intestinal macrophages in the human preterm intestine (fetus/premature neonate), but not in full-term neonates and adults, expressed inflammatory cytokines. Macrophage cytokine production was suppressed in the developing intestine by TGF-β, particularly the TGF-β(2) isoform. NEC was associated with decreased tissue expression of TGF-β(2) and decreased TGF-β bioactivity. In mice, disruption of TGF-β signaling worsened NEC-like inflammatory mucosal injury, whereas enteral supplementation with recombinant TGF-β(2) was protective.

Conclusions

Intestinal macrophages progressively acquire a noninflammatory profile during gestational development. TGF-β, particularly the TGF-β(2) isoform, suppresses macrophage inflammatory responses in the developing intestine and protects against inflammatory mucosal injury. Enterally administered TGF-β(2) protected mice from experimental NEC-like injury."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2010.09.043"xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Kelly D.R."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Jain S.K."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Shimamura M."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Bhandari V."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Serra R."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Athar M."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Ambalavanan N."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Maheshwari A."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Murphy-Ullrich J."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Dimmitt R.A."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Nicola T."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Ohls R.K."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/author"Aprahamian C."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/name"Gastroenterology"xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/pages"242-253"xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/title"TGF-beta2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine."xsd:string
http://purl.uniprot.org/citations/20875417http://purl.uniprot.org/core/volume"140"xsd:string
http://purl.uniprot.org/citations/20875417http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20875417
http://purl.uniprot.org/citations/20875417http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20875417
http://purl.uniprot.org/uniprot/P10145#attribution-B5D396ED6FE72DF99847E4D0910354BChttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20875417
http://purl.uniprot.org/uniprot/P10600#attribution-708BCECA9B3359B6F7E4B1CDD5D2644Ahttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20875417
▶