PMID- 21240009
OWN - NLM
STAT- MEDLINE
DCOM- 20110606
LR  - 20171116
IS  - 1536-4801 (Electronic)
IS  - 0277-2116 (Linking)
VI  - 52
IP  - 2
DP  - 2011 Feb
TI  - Ileal immune dysregulation in necrotizing enterocolitis: role of CD40/CD40L in 
      the pathogenesis of disease.
PG  - 140-6
LID - 10.1097/MPG.0b013e3182039bad [doi]
AB  - OBJECTIVES: CD40, a co-stimulatory molecule, plays a critical role in 
      coordinating enteric inflammatory immune responses. In necrotizing enterocolitis 
      (NEC), upregulation of IL-10, a CD40-modulated cytokine, has been described, but 
      the role of the IL-10 receptor (IL-10Rbeta), CD40, and its ligand CD40L in disease 
      pathogenesis is unknown. The study herein investigates ileal expression of CD40, 
      CD40L, and IL-10R in a rat model of NEC. SUBJECTS AND METHODS: NEC was induced in 
      newborn rats using established methods of formula feeding, asphyxia, and cold 
      stress. Expression of CD40, CD40L, IL-10Rbeta, and other proinflammatory molecules, 
      including Toll-like receptor-4 (TLR-4) and IL-18, was assessed by immunoblotting. 
      Tissue infiltration by macrophages, monocytes, and T cells was examined by 
      confocal immunohistochemistry. RESULTS: Ileum from rat pups with NEC showed 
      increased expression of TLR-4, IL-18, and IL-10Rbeta. Sections from both NEC and 
      control pups demonstrated preservation of ileal cells expressing CD40/CD40L. The 
      distal ileum of controls expressed both CD40 and CD40L; conversely, neither 
      molecule was detected in ileal tissue from NEC pups. Additional studies showed 
      that treatment with epidermal growth factor (EGF), previously shown to ameliorate 
      the severity of NEC in an animal model, did not restore CD40 expression. 
      CONCLUSIONS: Ileal cytokine dysregulation, manifested by decreased CD40/CD40L and 
      increased IL-10Rbeta expression, may be involved in the pathogenesis of NEC. 
      Dampened CD40 signaling may be related to enhanced IL-10 expression and a 
      suppressed T-cell response to injury. We speculate that augmenting CD40-CD40L 
      interactions may achieve a protective effect in this NEC model.
FAU - Xu, Jiliu
AU  - Xu J
AD  - Division of Pediatric Gastroenterology, USA.
FAU - Treem, William R
AU  - Treem WR
FAU - Roman, Christopher
AU  - Roman C
FAU - Anderson, Virginia
AU  - Anderson V
FAU - Rubenstein, Richard
AU  - Rubenstein R
FAU - Schwarz, Steven M
AU  - Schwarz SM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pediatr Gastroenterol Nutr
JT  - Journal of pediatric gastroenterology and nutrition
JID - 8211545
RN  - 0 (CD40 Antigens)
RN  - 0 (IL10RB protein, human)
RN  - 0 (Interleukin-10 Receptor beta Subunit)
RN  - 0 (Interleukin-18)
RN  - 0 (Toll-Like Receptor 4)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - CD40 Antigens/drug effects/*immunology/metabolism
MH  - CD40 Ligand/metabolism
MH  - Enterocolitis, Necrotizing/etiology/*immunology/metabolism
MH  - Epidermal Growth Factor/pharmacology
MH  - Ileum/*immunology/metabolism/pathology
MH  - Inflammation/*immunology
MH  - Interleukin-10 Receptor beta Subunit/drug effects/*immunology/metabolism
MH  - Interleukin-18/metabolism
MH  - Macrophages/immunology/metabolism
MH  - Models, Animal
MH  - Monocytes/immunology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - T-Lymphocytes/immunology/metabolism
MH  - Toll-Like Receptor 4/metabolism
EDAT- 2011/01/18 06:00
MHDA- 2011/06/07 06:00
CRDT- 2011/01/18 06:00
PHST- 2011/01/18 06:00 [entrez]
PHST- 2011/01/18 06:00 [pubmed]
PHST- 2011/06/07 06:00 [medline]
AID - 10.1097/MPG.0b013e3182039bad [doi]
PST - ppublish
SO  - J Pediatr Gastroenterol Nutr. 2011 Feb;52(2):140-6. doi: 
      10.1097/MPG.0b013e3182039bad.