NOD2-and disease-specific gene expression profiles of peripheral blood mononuclear cells from Crohn's disease patients

作     者：Holger Schufler Maria Rohde Sarah Rohde Astrid Huth Nicole Gittel Hannes Hollborn Dirk Koczan Ane Glass Georg Lamprecht Robert Jaster 

作者机构：Department of Medicine IIDivision of GastroenterologyRostock University Medical CenterRostock 18057Germany Institute of ImmunologyRostock University Medical CenterRostock 18057Germany Institute for Biostatistics and Informatics in Medicine and Ageing ResearchRostock 18057Germany 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2018年第24卷第11期

页      面：1196-1205页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by a grant from the Damp-Foundation(2016-04) to Schaffler H and Rohde S 

主　　题：Peripheral blood mononuclear cells Gene expression NOD2 Lysozyme Crohn's disease CLEC5A 

摘      要：AIM To investigate disease-specific gene expression profiles of peripheral blood mononuclear cells(PBMCs) from Crohn s disease(CD) patients in clinical *** Patients with CD in clinical remission or with very low disease activity according to the Crohn s disease activity index were genotyped regarding nucleotidebinding 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 *** 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 realtime ***2-and disease-specific gene expression profiles were evaluated with repeated measure ANOVA by a general linear *** 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 *** 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,CLEC5 A(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;CLEC5 A,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 *** Our data identify CLEC5 A and LYZ as CD-and NOD2-associated genes of PBMCs and encourage further studies on their pathomechanistic roles.