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Expression of human beta-defensins in children with chronic inflammatory bowel disease.

Zilbauer M, Jenke A, Wenzel G, Postberg J, Heusch A, Phillips AD, Noble-Jamieson G, Torrente F, Salvestrini C, Heuschkel R, Wirth S - PLoS ONE (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, HELIOS Klinikum Wuppertal, Germany. mz304@medschl.cam.ac.uk

ABSTRACT

Background: Human 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.

Methods: Intestinal 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.

Results: Significant 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.

Conclusion: Our 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.

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Related in: MedlinePlus

Expression of hBDs and inflammatory cytokines in the intestinal mucosa of healthy children.Biopsies were obtained from duodenum (D), terminal ileum (TI) and ascending colon (AC). Absolute mRNA copy number for hBD1-3 (a-c), IL-8 (d) and TNF-alpha (e) in each biopsy were quantified by real-time PCR using the standard curve method. Expression levels were normalized against the geometrical mean of two selected housekeeping genes (GPDH and β-actin). Data is expressed as the mean ± standard error of mean (SEM). The number of biopsies analysed for each patient group is stated (n). Values for P<0.05 were considered to be statistically significant.
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pone-0015389-g001: Expression of hBDs and inflammatory cytokines in the intestinal mucosa of healthy children.Biopsies were obtained from duodenum (D), terminal ileum (TI) and ascending colon (AC). Absolute mRNA copy number for hBD1-3 (a-c), IL-8 (d) and TNF-alpha (e) in each biopsy were quantified by real-time PCR using the standard curve method. Expression levels were normalized against the geometrical mean of two selected housekeeping genes (GPDH and β-actin). Data is expressed as the mean ± standard error of mean (SEM). The number of biopsies analysed for each patient group is stated (n). Values for P<0.05 were considered to be statistically significant.

Mentions: 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 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). In addition to beta-defensins we also analysed mucosal expression of inflammatory cytokines IL-8 and TNF-alpha. As shown in Figure 1d and e, significantly higher levels for both IL-8 (P = 0.0222) and TNF-alpha (P = 0.0014) were found in the healthy TI compared to duodenum and ascending colon.


Expression of human beta-defensins in children with chronic inflammatory bowel disease.

Zilbauer M, Jenke A, Wenzel G, Postberg J, Heusch A, Phillips AD, Noble-Jamieson G, Torrente F, Salvestrini C, Heuschkel R, Wirth S - PLoS ONE (2010)

Expression of hBDs and inflammatory cytokines in the intestinal mucosa of healthy children.Biopsies were obtained from duodenum (D), terminal ileum (TI) and ascending colon (AC). Absolute mRNA copy number for hBD1-3 (a-c), IL-8 (d) and TNF-alpha (e) in each biopsy were quantified by real-time PCR using the standard curve method. Expression levels were normalized against the geometrical mean of two selected housekeeping genes (GPDH and β-actin). Data is expressed as the mean ± standard error of mean (SEM). The number of biopsies analysed for each patient group is stated (n). Values for P<0.05 were considered to be statistically significant.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2962650&req=5

pone-0015389-g001: Expression of hBDs and inflammatory cytokines in the intestinal mucosa of healthy children.Biopsies were obtained from duodenum (D), terminal ileum (TI) and ascending colon (AC). Absolute mRNA copy number for hBD1-3 (a-c), IL-8 (d) and TNF-alpha (e) in each biopsy were quantified by real-time PCR using the standard curve method. Expression levels were normalized against the geometrical mean of two selected housekeeping genes (GPDH and β-actin). Data is expressed as the mean ± standard error of mean (SEM). The number of biopsies analysed for each patient group is stated (n). Values for P<0.05 were considered to be statistically significant.
Mentions: 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 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). In addition to beta-defensins we also analysed mucosal expression of inflammatory cytokines IL-8 and TNF-alpha. As shown in Figure 1d and e, significantly higher levels for both IL-8 (P = 0.0222) and TNF-alpha (P = 0.0014) were found in the healthy TI compared to duodenum and ascending colon.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, HELIOS Klinikum Wuppertal, Germany. mz304@medschl.cam.ac.uk

ABSTRACT

Background: Human 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.

Methods: Intestinal 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.

Results: Significant 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.

Conclusion: Our 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.

Show MeSH
Related in: MedlinePlus