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  • Title: Mucosal NOD2 expression and NF-kappaB activation in pediatric Crohn's disease.
    Author: Stronati L, Negroni A, Merola P, Pannone V, Borrelli O, Cirulli M, Annese V, Cucchiara S.
    Journal: Inflamm Bowel Dis; 2008 Mar; 14(3):295-302. PubMed ID: 18092345.
    Abstract:
    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-kappaB and a consequent proinflammatory cytokine production. The present study was aimed at investigating the expression and activity of NOD2, NF-kappaB, and of 2 proinflammatory cytokines, TNFalpha and IL-1beta, 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-kappaB binding activity was assessed by electromobility gel shift assay (EMSA). RESULTS: NOD2 and IL-1beta mRNAs were upregulated in CD children. Protein levels of NOD2, TNFalpha, and nuclear NF-kappaB, as well as the binding activity of NF-kappaB to a consensus DNA sequence, were significantly increased in inflamed mucosa of patients as compared to controls. Moreover, NF-kappaB activity was strongly upregulated in patients also when bound to the NOD2 promoter site. No difference was seen between patients and controls when NF-kappaB binding activity was determined in the uninflamed tissue. CONCLUSIONS: This study suggests that altered mechanisms regulating NOD2 induction, NF-kappaB activation and cytokine production may contribute to dysregulate the innate immune response underlying pediatric CD.
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