Abstract
BackgroundHuman beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children.MethodsIntestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohn's disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative real-time (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha.ResultsSignificant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohn's disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon.ConclusionOur study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD, lending further support for their potential role in disease pathogenesis.
Highlights
Human beta-defensins are a group of evolutionarily conserved antimicrobial peptides (AMPs) known to play a major role in innate host defence at various mucosal surfaces including the gastrointestinal (GI) tract
First we analysed expression of hBD1-3 throughout the intestinal tract of healthy children. hBD1 was expressed constitutively in small and large bowel biopsies with levels being significantly higher in the colon compared to duodenum and terminal ileum (TI) (Figure 1a)
In contrast to hBD1, inducible defensins hBD2 and -3 were infrequently expressed, with low copy numbers and no significant differences between bowel segments (Figure 1a and b)
Summary
Human beta-defensins (hBDs) are a group of evolutionarily conserved antimicrobial peptides (AMPs) known to play a major role in innate host defence at various mucosal surfaces including the gastrointestinal (GI) tract. HBD1 is expressed constitutively by intestinal epithelial cells while hBD2 and -3 are induced during infection and inflammation [1,2] In addition to their potent antimicrobial properties against commensal and pathogenic bacteria [3,4], betadefensins have been shown to function as multieffector molecules capable of enhancing host defence by recruiting various innate as well as adaptive immune cells to the site of infection, induction of neovasculogenesis and enhancing wound closure [5,6,7]. Little is known about expression of these peptides in children
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