Abstract:
BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/CARD15. The aim was to test whether defensins and cathelicidin (LL-37) expression and NOD2/CARD15 mutations in blood neutrophils are related to molecular bacterial translocation events in CD patients. METHODS:Fifty consecutively admitted CD patients and 15 healthy controls were included. Clinical and analytical characteristics of patients were considered. NOD2/CARD15 genotyping, presence of bacterial-DNA, defensin and cathelicidin gene, and protein levels in neutrophils and serum cytokine levels were studied. RESULTS:Twenty patients (40%) presented bacterial-DNA in blood. Eleven were active and 9 were in remission. Bacterial-DNA was not present in controls. NOD2/CARD15 mutations were identified in 25 patients (50%), 15 of which were in remission. Sixty percent of bacterial-DNA(+) and 43% of bacterial-DNA(-) patients showed a NOD2/CARD15 mutation. β-Defensin 2 and LL-37 mRNA and protein levels were upregulated in bacterial-DNA(+) patients. β-Defensin 2 and LL-37 expression correlated with bacterial-DNA concentration only in patients with a wildtype NOD2/CARD15 genotype. Cultured neutrophils of bacterial-DNA(-) patients confirmed the muramyl dipeptide-independent association between DEFB2 and LL-37 with bacterial-DNA concentration in wildtype NOD2/CARD15 patients. Cytokine levels were increased in bacterial-DNA(+) patients and correlated with bacterial-DNA concentration. NOD2/CARD15 genotype did not influence this correlation. CONCLUSIONS:β-Defensin 2, LL-37, and proinflammatory cytokines are increased in CD patients with bacterial-DNA in a concentration-dependent manner. NOD2/CARD15 plays a key role in the regulation of this response.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Gutiérrez A,Holler E,Zapater P,Sempere L,Jover R,Pérez-Mateo M,Schoelmerich J,Such J,Wiest R,Francés Rdoi
10.1002/ibd.21537subject
Has Abstractpub_date
2011-08-01 00:00:00pages
1641-50issue
8eissn
1078-0998issn
1536-4844journal_volume
17pub_type
杂志文章abstract:BACKGROUND:Previous research suggests a link between childhood adversities and inflammatory bowel disease (IBD); however, study limitations prevent generalization of findings. To address this, the current study uses a Canadian population-based sample to investigate the relationship between 3 childhood adversities and 2...
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journal_title:Inflammatory bowel diseases
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journal_title:Inflammatory bowel diseases
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journal_title:Inflammatory bowel diseases
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章,meta分析
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pub_type: 临床试验,杂志文章,随机对照试验
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