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.
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 CDpatients. METHODS: Fifty consecutively admitted CDpatients 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/CARD15patients. 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 CDpatients with bacterial-DNA in a concentration-dependent manner. NOD2/CARD15 plays a key role in the regulation of this response.
Authors: Ana Gutiérrez; Pedro Zapater; Oriol Juanola; Laura Sempere; Marifé García; Raquel Laveda; Antonio Martínez; Michael Scharl; José M González-Navajas; José Such; Reiner Wiest; Gerhard Rogler; Rubén Francés Journal: Am J Gastroenterol Date: 2016-02-23 Impact factor: 10.864
Authors: S Kusaka; A Nishida; K Takahashi; S Bamba; H Yasui; M Kawahara; O Inatomi; M Sugimoto; A Andoh Journal: Clin Exp Immunol Date: 2017-09-28 Impact factor: 4.330
Authors: Paula Piñero; Oriol Juanola; Ana Gutiérrez; Pedro Zapater; Paula Giménez; Anna Steinert; Laura Sempere; José M González-Navajas; Jan H Niess; Rubén Francés Journal: J Mol Med (Berl) Date: 2017-09-06 Impact factor: 4.599
Authors: Oriol Juanola; Alba Moratalla; Ana Gutiérrez; Laura Sempere; Pedro Zapater; Paula Giménez; Isabel Almenta; Gloria Peiró; José M González-Navajas; José F Such; Rubén Francés Journal: J Gastroenterol Date: 2014-12-11 Impact factor: 7.527
Authors: E Cerrillo; I Moret; M Iborra; D Ramos; E Busó; L Tortosa; E Sáez-González; P Nos; B Beltrán Journal: Clin Exp Immunol Date: 2018-01-10 Impact factor: 4.330
Authors: Jeffrey P Meisch; Michiko Nishimura; Ryan M Vogel; Hannah C Sung; Beth A Bednarchik; Santosh K Ghosh; Pingfu Fu; Thomas McCormick; Aaron Weinberg; Alan D Levine Journal: Inflamm Bowel Dis Date: 2013-04 Impact factor: 5.325