DOI: 10.1097/01.mpg.0000256199.96838.56

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Issn Print: 0277-2116

Publication Date: 2006/11/01


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Expression of mRNA and Protein of Toll-like Receptors 2 and 4 Are Upregulated in Children with IBD

G Veres; B Szebeni; M Mraz; A Dezsofi; A Vannay; B Vasarhelyi; E Majorova; A Arato

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Author Information: First Department of Paediatrics, Semmelweis University, Budapest, Hungary

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Excerpt

Background/aim: Chronic inflammation in inflammatory bowel disease (IBD) may result from exaggerated stimulation of the mucosal immune system by the endogenous luminal bacterial flora. Bacterial products are recognized by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), which are key regulators of the innate immune system. Therefore, the expression of TLR2, TLR3 and TLR4 in colonic biopsy samples taken from children with active IBD were studied and compared to controls.
Methods: Colonic biopsy specimens were collected from 12 children [median (range): 13 (6-18) yr] with newly diagnosed IBD (n-IBD) and 23 children [15 (8-18) yr] with relapsed IBD on treatment (r-IBD) from macroscopically involved and noninvolved mucosa. Specimens were also obtained from 8 controls [median (range): 14 (6-16) yr]. TLR2, TLR3 and TLR4 mRNA, and - related protein expression were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively.
Results: The TLR2 and TLR4 mRNA expression were significantly increased in the involved colonic mucosa of children with n-IBD and r-IBD compared to controls, respectively (p<0.05). We found higher TLR2 and TLR4 mRNA expression in the involved vs. noninvolved colonic mucosa of children with n-IBD and r-IBD, respectively (p<0.05). TLR2 protein expression in the involved mucosa of patients with n-IBD and r-IBD were 8.9 and 8.5 times higher than controls, respectively (p<0.001 and p<0.0001). Involved mucosa in children with n-IBD and r-IBD depicted 5-fold and 4.5-fold elevation of TLR4 protein expression in comparison to controls, respectively (p<0.001 and p<0.0001). In the noninvolved mucosa of children with n-IBD and r-IBD, TLR2 and TLR4 mRNA and protein expression were similar to controls. The TLR3 mRNA and protein expression were similar in all groups studied.
Summary/conclusions: Our results of increased expression of TLR2 and TLR4 in the inflamed colonic mucosa of children with IBD confirm the hypothesis that innate immunity has an important role in the pathogenesis of this disease. Nevertheless, the similar expression of these PRRs in the noninvolved colonic mucosa in children with IBD and in controls does not support their primary role in the development of IBD.
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