Mucosal NOD2 expression and NF-κB activation in pediatric Crohn's disease

✍ Scribed by Laura Stronati; Anna Negroni; Paola Merola; Veronica Pannone; Osvaldo Borrelli; Manuela Cirulli; Vito Annese; Salvatore Cucchiara

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 278 KB
• Volume: 14
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20332

✦ Synopsis

Background:

Recent advances in the pathogenesis of Crohn's disease (CD) have suggested that an aberrant innate immune response initiates the cascade of events leading to T-cell activation and to disease development. NOD2 protein, which is mainly expressed by innate immunity cells, appears to play a key role against bacteria by triggering a host defense response through the activation of the transcriptor factor NF-B and a consequent proinflammatory cytokine production. The present study was aimed at investigating the expression and activity of NOD2, NF-B, and of 2 proinflammatory cytokines, TNF␣ and IL-1␤, in mucosal biopsies of CD affected children compared to healthy controls.

Methods:

In all, 22 children with active CD and 10 matched controls were entered in the study. mRNA and protein expressions were detected using reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot; NF-B binding activity was assessed by electromobility gel shift assay (EMSA).

Results: NOD2 and IL-1␤ mRNAs were upregulated in CD children. Protein levels of NOD2, TNF␣, and nuclear NF-B, as well as the binding activity of NF-B to a consensus DNA sequence, were significantly increased in inflamed mucosa of patients as compared to controls. Moreover, NF-B activity was strongly upregulated in patients also when bound to the NOD2 promoter site. No difference was seen between patients and controls when NF-B binding activity was determined in the uninflamed tissue.

Conclusions:

This study suggests that altered mechanisms regulating NOD2 induction, NF-B activation and cytokine production may contribute to dysregulate the innate immune response underlying pediatric CD.