Genome-wide gene expression analysis for target genes to differentiate patients with intestinal tuberculosis and Crohn's disease and discriminative value of FOXP3 mRNA expression.

作者: Vineet Ahuja , Swati Subodh , Amit Tuteja , Veena Mishra , Sushil Kumar Garg

DOI: 10.1093/GASTRO/GOV015

关键词:

摘要: Background and aims: Crohn’s disease (CD) intestinal tuberculosis (ITB) are both chronic granulomatous conditions with similar phenotypic presentations. Hence, there is need for a biomarker to differentiate between these two diseases. This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases ITB CD in comparison controls. To evaluate the role T regulatory cells, forkhead box P3 (FOXP3) mRNA was quantified serum as well patients Methods: Paired samples, including biopsies, were taken 33 subjects (CD, controls), total RNA extracted. Human whole genome microarray performed using Illumina HumanWG-6 BeadChip Kit six samples three groups duplicates. Real-time PCR FOXP3 analyzed biopsy (4-CD, 5-ITB, 4-controls). Results: In 1.5-fold upregulation 92 382 genes downregulation 91 256 genes, respectively. Peroxisome proliferators via PPARc pathway most significantly downregulated (P 2-fold change. ITB, complement activation pathway, specifically classical upregulated. elevated obtained compared (4.70 6 2.21 vs 1.48 0.31, P ¼ 0.016). Conclusions: mucosa could be discriminatory marker CD. Upregulation suggests that pathogenetic mechanisms those pulmonary tuberculosis. CD, seen tissue, suggesting restoration PPARc-dependent anti-microbial barrier function may therapeutic target.

参考文章(37)
Sayma Rahman, Berhanu Gudetta, Joshua Fink, Anna Granath, Senait Ashenafi, Abraham Aseffa, Milliard Derbew, Mattias Svensson, Jan Andersson, Susanna Grundström Brighenti, Compartmentalization of Immune Responses in Human Tuberculosis The American Journal of Pathology. ,vol. 174, pp. 2211- 2224 ,(2009) , 10.2353/AJPATH.2009.080941
Yasunari Takada, Neelanjan Ray, Eiji Ikeda, Tomohiro Kawaguchi, Masayoshi Kuwahara, Erwin F Wagner, Koichi Matsuo, None, Fos Proteins Suppress Dextran Sulfate Sodium-Induced Colitis through Inhibition of NF-κB Journal of Immunology. ,vol. 184, pp. 1014- 1021 ,(2010) , 10.4049/JIMMUNOL.0901196
S. Burl, P. C. Hill, D. J. Jeffries, M. J. Holland, A. Fox, M. D. Lugos, R. A. Adegbola, G. A. Rook, A. Zumla, K. P. W. J. McAdam, R. H. Brookes, FOXP3 gene expression in a tuberculosis case contact study. Clinical and Experimental Immunology. ,vol. 149, pp. 117- 122 ,(2007) , 10.1111/J.1365-2249.2007.03399.X
Bo Wu, Chunhong Huang, Midori Kato-Maeda, Philip C Hopewell, Charles L Daley, Alan M Krensky, Carol Clayberger, None, Messenger RNA Expression of IL-8, FOXP3, and IL-12β Differentiates Latent Tuberculosis Infection from Disease Journal of Immunology. ,vol. 178, pp. 3688- 3694 ,(2007) , 10.4049/JIMMUNOL.178.6.3688
Sarah L. Doyle, Luke A.J. O’Neill, Toll-like receptors: From the discovery of NFκB to new insights into transcriptional regulations in innate immunity Biochemical Pharmacology. ,vol. 72, pp. 1102- 1113 ,(2006) , 10.1016/J.BCP.2006.07.010
Maria V. Carroll, Nathan Lack, Edith Sim, Anders Krarup, Robert B. Sim, Multiple routes of complement activation by Mycobacterium bovis BCG Molecular Immunology. ,vol. 46, pp. 3367- 3378 ,(2008) , 10.1016/J.MOLIMM.2009.07.015
Christine M Costello, Nancy Mah, Robert Häsler, Philip Rosenstiel, Georg H Waetzig, Andreas Hahn, Tim Lu, Yesim Gurbuz, Susanna Nikolaus, Mario Albrecht, Jochen Hampe, Ralph Lucius, Günther Klöppel, Holger Eickhoff, Hans Lehrach, Thomas Lengauer, Stefan Schreiber, Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays. PLOS Medicine. ,vol. 2, pp. 1- 17 ,(2005) , 10.1371/JOURNAL.PMED.0020199
L. Peyrin-Biroulet, J. Beisner, G. Wang, S. Nuding, S. T. Oommen, D. Kelly, E. Parmentier-Decrucq, R. Dessein, E. Merour, P. Chavatte, T. Grandjean, A. Bressenot, P. Desreumaux, J.-F. Colombel, B. Desvergne, E. F. Stange, J. Wehkamp, M. Chamaillard, Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 8772- 8777 ,(2010) , 10.1073/PNAS.0905745107