title: Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis.
abstract: It is unclear whether the broad inflammatory response shown in neonatal necrotizing enterocolitis (NEC) is the cause or the effect of tissue injury. Toll-like receptors (TLRs) on intestinal dendritic, mononuclear, and epithelial cells recognize bacterial ligands and damaged tissues, thus activating the inflammatory response. The present study aimed to determine whether active TLR signaling would precede histological injury in NEC. Newborn rat pups were divided into four groups: dam fed, dam fed-hypoxic, formula fed, and formula fed-hypoxic (NEC). The ileal tissues were evaluated for NEC scores at 24, 48, 72, and 120 h. Quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure and localize intestinal TLRs. Cytokines were assessed by a multispot cytokine array. Among the four groups, ileal injury was seen only after 72 h of formula feeding and hypoxia. We found selective induction of mRNA levels in NEC compared with dam-fed controls for TLR2 > TLR4 > TLR1 = TLR3, TLR7, and TLR9 > TLR6 (P < 0.01); TLR5 was downregulated (P < 0.01). All TLR changes started at 48 h, before any histological evidence of NEC. Both Th1-type cytokines (IFN-gamma, IL-1beta, TNF-alpha, and KC/GRO) and Th2-type cytokines (IL-4, IL-5 and IL-13) were significantly increased in NEC but also in nondamaged formula-fed rat ileum. In conclusion, the intestinal expression of TLRs and cytokines precedes histological injury in the experimental NEC.
authors.affiliation: Department of Pediatrics, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.forename: Limin
authors.initials: L
authors.lastname: Zhu
authors.forename: Nicole Y
authors.initials: NY
authors.lastname: Fatheree
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Pacheco
authors.forename: Nina
authors.initials: N
authors.lastname: Tatevian
authors.forename: Jon Marc
authors.initials: JM
authors.lastname: Rhoads
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000276:immunology* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000276:immunology; D007082:Ileum / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D041943:Infant Formula; D007231:Infant, Newborn; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051193:Toll-Like Receptors