Journal
INFLAMMATORY BOWEL DISEASES
Volume 16, Issue 1, Pages 68-75Publisher
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.20995
Keywords
inflammatory bowel disease; necrotizing enterocolitis; TLR4; MD-2; immunohistochemistry; laser capture microdissection
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Funding
- AGIKO-stipendium [920-03-438]
- Netherlands Organization for Health Researchand Development
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI032738] Funding Source: NIH RePORTER
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Background: Microbiota in the intestinal lumen provide an abundant source of potentially detrimental antigens, including lipopolysaccharide (LIPS), a potent immunostimulatory product of Gram-negative bacteria recognized by the host via TLR-4 and MD-2, An aberrant immune response to LPS or other bacterial antigens has been linked to inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). Methods: We investigated which cells express MD-2 in the not-trial and inflamed ileum from neonates and adults by immunohistochemistry. Moreover, MD-2 and TLR4 mRNA expression in normal adult ileum was studied by reverse-transcription polymerase chain reaction (RT-PCR) on cells isolated by laser capture microdissection. Results: premature infants did not show MD-2 expression either in epithelial cells or in the lamina propria. Similarly, MD-2 was absent in epithelial cells and lamina propria inflammatory cells in preterm infants with NEC. MD-2 protein in the healthy term neonatal and adult ileum was predominantly expressed by Paneth cells and some resident inflammatory cells in the lamina propria. MD-2 and TLR-4 mRNA expression was restricted to crypt cells. Also in IBD, Paneth cells were still the sole MD-2-expressing epithelial cells, whereas inflammatory cells (mainly plasma cells) were responsible for the vast majority of the MD-2 expression. Conclusions: The absence of MD-2 in the miniature neonatal out suggests impaired LPS sensing, which could predispose neonates to NEC upon microbial colonization of the immature intestine. The apparent expression of MD-2 by Paneth cells supports the critical concept that these cells respond to luminal bacterial products in order to maintain homeostasis with the intestinal microbiota in vivo.
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