title: Toll-like receptor-4 in human and mouse colonic epithelium is developmentally regulated: a possible role in necrotizing enterocolitis.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) is an immature intestinal condition resulting in devastating intestinal inflammation due to unknown mechanisms. Evidence has suggested that intestinal maturation attenuates the severity of NEC and Toll-like receptor 4 (TLR4) has been suggested to play a critical role in its pathogenesis. We investigated whether maturational effects of TLR4 expression in immature colon might contribute to the development of NEC.
  
  
  METHODS
  TLR4 colonocyte expression was detected by immunofluorescence confocal microscopy. Interleukin-6 (IL-6) levels were assayed by an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  TLR4 expression was high in fetal colonic epithelium in human and mouse, with earlier gestation having a higher surface/cytoplasm distribution. TLR4 remained high in mouse postnatal day 1 but the surface/cytoplasm distribution was reduced. TLR4 decreased in amount and then was expressed in crypts in the mature human and mouse colon. Hydrocortisone (HC) reduced the surface/cytoplasm distribution of TLR4 in human fetal colon. Elevated IL-6 levels in immature colon after lipopolysaccharide were attenuated by HC in human and mouse.
  
  
  CONCLUSIONS
  Expression, localization, and signaling of TLR4 in colonic epithelium may be developmentally regulated. HC may accelerate the TLR developmental pathway change to an adult type, which may account for its impact on TLR4 signaling.
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Di
authors.initials: D
authors.lastname: Meng
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Weishu
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Hai Ning
authors.initials: HN
authors.lastname: Shi
authors.affiliation: Section of Neonatology, Department of Pediatrics and Medicine, The University of Chicago, Chicago, Illinois.
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Vasuki
authors.initials: V
authors.lastname: Wijendran
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Winber
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: W Allan
authors.initials: WA
authors.lastname: Walker
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology*; D020345:Enterocolitis, Necrotizing / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D006854:Hydrocortisone