Abstract:
AIM:To investigate disease-specific gene expression profiles of peripheral blood mononuclear cells (PBMCs) from Crohn's disease (CD) patients in clinical remission. METHODS:Patients with CD in clinical remission or with very low disease activity according to the Crohn's disease activity index were genotyped regarding nucleotide-binding oligomerization domain 2 (NOD2), and PBMCs from wild-type (WT)-NOD2 patients, patients with homozygous or heterozygous NOD2 mutations and healthy donors were isolated for further analysis. The cells were cultured with vitamin D, peptidoglycan (PGN) and lipopolysaccharide (LPS) for defined periods of time before RNA was isolated and subjected to microarray analysis using Clariom S assays and quantitative real-time PCR. NOD2- and disease-specific gene expression profiles were evaluated with repeated measure ANOVA by a general linear model. RESULTS:Employing microarray assays, a total of 267 genes were identified that were significantly up- or downregulated in PBMCs of WT-NOD2 patients, compared to healthy donors after challenge with vitamin D and/or a combination of LPS and PGN (P < 0.05; threshold: ≥ 2-fold change). For further analysis by real-time PCR, genes with known impact on inflammation and immunity were selected that fulfilled predefined expression criteria. In a larger cohort of patients and controls, a disease-associated expression pattern, with higher transcript levels in vitamin D-treated PBMCs from patients, was observed for three of these genes, CLEC5A (P < 0.030), lysozyme (LYZ; P < 0.047) and TREM1 (P < 0.023). Six genes were found to be expressed in a NOD2-dependent manner (CD101, P < 0.002; CLEC5A, P < 0.020; CXCL5, P < 0.009; IL-24, P < 0.044; ITGB2, P < 0.041; LYZ, P < 0.042). Interestingly, the highest transcript levels were observed in patients with heterozygous NOD2 mutations. CONCLUSION:Our data identify CLEC5A and LYZ as CD- and NOD2-associated genes of PBMCs and encourage further studies on their pathomechanistic roles.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Schäffler H,Rohde M,Rohde S,Huth A,Gittel N,Hollborn H,Koczan D,Glass Ä,Lamprecht G,Jaster Rdoi
10.3748/wjg.v24.i11.1196subject
Has Abstractpub_date
2018-03-21 00:00:00pages
1196-1205issue
11eissn
1007-9327issn
2219-2840journal_volume
24pub_type
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journal_title:World journal of gastroenterology
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journal_title:World journal of gastroenterology
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journal_title:World journal of gastroenterology
pub_type: 临床试验,杂志文章
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journal_title:World journal of gastroenterology
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pub_type: 杂志文章,评审
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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journal_title:World journal of gastroenterology
pub_type: 社论,评审
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pub_type: 杂志文章
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journal_title:World journal of gastroenterology
pub_type: 杂志文章,评审
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更新日期:2014-05-21 00:00:00
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