期刊论文详细信息
BMC Research Notes
A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide
Flavio F Nobre1  Euzenir N Sarno2  Ulisses G Lopes3  Elizabeth P Sampaio2  Daniel Serra de Carvalho2  Jorgenilce de Souza Sales2  Tatiana O Fulco2  Alessandra M Saliba4  Renata T Paiva1 
[1]Biomedical Engineering Program, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
[2]Leprosy Laboratory, Institute Oswaldo Cruz, Rio de Janeiro, Brazil
[3]Department of Molecular and Structural Biology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
[4]Department of Microbiology, Immunology and Parasitology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
关键词: Lipopolysaccharide;    Inflammation model;    Rank product;    Microarray;    Thalidomide;   
Others  :  1166311
DOI  :  10.1186/1756-0500-5-292
 received in 2012-04-06, accepted in 2012-05-30,  发布年份 2012
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【 摘 要 】

Background

Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS) stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide.

Results

We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR.

Conclusions

The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

【 授权许可】

   
2012 Paiva et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]von Moos R, Stolz R, Cerny T, Gillessen S: Thalidomide: from tragedy to promise. Swiss Med. Wkly. 2003, 133(5/6):77-87.
  • [2]Wu JJ, Huang DB, Pang KR, Hsu S, Tyring SK: Thalidomide: dermatological indications, mechanisms of action and side-effects. Brit. J. Dermatol. 2005, 153(2):254-273.
  • [3]Teo SK: Properties of thalidomide and its analogues: implications for anticancer therapy. AAPS J 2005, 7(1):14-19.
  • [4]Sampaio EP, Carvalho DS, Nery JAC, Lopes UG, Sarno EN: Thalidomide: an overview of its pharmacological mechanisms of action. Curr. Med. Chem 5th edition. 2006, 71-77.
  • [5]Fujita K, Asami Y, Tanaka K, Akita M, Merker H-J: Anti-angiogenic effects of thalidomide: expression of apoptosis-inducible active-caspase-3 in a three-dimensional collagen gel ulture of aorta. Histochem. Cell Biol 2004, 122(1):-.
  • [6]Tadesse A, Shannon EJ: Effects of thalidomide on intracellular Mycobacterium leprae in normal and activated macrophages. Clin Vaccine Immunol 2005, 12(1):130-130.
  • [7]Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G: Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J. Exp. Med. 1991, 173(3):699-699.
  • [8]Haslett PAJ, Roche P, Butlin CR, Macdonald M, Shrestha N, Manandhar R, LeMaster J, Hawksworth R, Shah M, Lubinsky AS, et al.: Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation. J Infect Dis 2005, 192:2045-2053.
  • [9]Lagier JC, Fenollar F, Lepidi H, Liozon E, Raoult D: Successful treatment of immune reconstitution inflammatory syndrome in Whipple's disease using Thalidomide. J. Infection 2010, 60(1):79-82.
  • [10]Majumdar S, Lamothe B, Aggarwal BB: Thalidomide Suppresses NF-kappa B Activation Induced by TNF and H2O2, But Not That Activated by Ceramide, Lipopolysaccharides, or Phorbol Ester. J Immunol 2002, 168(6):2644-2651.
  • [11]Baldwin AS: The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996, 14(1):649-681.
  • [12]Kirschning CJ, Wesche H, Ayres TM, Rothe M: Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide. J. Exp. Med. 1998, 188(11):2091-2097.
  • [13]Moreira AL, Sampaio E, Zmuidzinas A, Frindt P, Smith KA, Kaplan G: Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J. Exp. Med. 1993, 177(6):1675-1168.
  • [14]Quackenbush J: Microarray data normalization and transformation. Nat Genet 2002, 32:496-501.
  • [15]Butte A: The use and analysis of microarray data. Nat. Rev. Drug Discovery 2002, 1(12):951-960.
  • [16]Crowther DJ: Applications of microarrays in the pharmaceutical industry. Curr Opin Pharmacol 2002, 2(5):551-554.
  • [17]Brazma A, Vilo J: Gene expression data analysis. Microbes Infect. 2001, 3(10):823-829.
  • [18]Breitling R, Armengaud P, Amtmann A, Herzyk P: Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 2004, 573(1–3):83-92.
  • [19]Sharif O, Bolshakov VN, Raines S, Newham P, Perkins ND: Transcriptional profiling of the LPS induced NF-κB response in macrophages. BMC Immunol 2007, 8(1):1-1. BioMed Central Full Text
  • [20]Lee DJ, Li H, Ochoa MT, Tanaka M, Carbone RJ, Damoiseaux R, Burdick A, Sarno EN, Rea TH, Modlin RL: Integrated Pathways for Neutrophil Recruitment and Inflammation in Leprosy. J Infect Dis 2010, 201(4):558-569.
  • [21]Falcon S, Gentleman R: Using GOstats to test gene lists for GO term association. Bioinformatics 2007, 23(2):257-258.
  • [22]Ng SSW, MacPherson GR, Gütschow M, Eger K, Figg WD: Antitumor Effects of Thalidomide Analogs in Human Prostate Cancer Xenografts Implanted in Immunodeficient Mice. Clin. Cancer Res 2004, 10(12):4192-4197.
  • [23]Liu WM, Strauss SJ, Chaplin T, Shahin S, Propper DJ, Young BD, Joel SP, Malpas JS: s-Thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line. Hematol J 2004, 5(3):247-254.
  • [24]Kumar S, Greipp PR, Haug J, Kline M, Chng WJ, Blood E, Bergsagel L, Lust JA, Gertz MA, Fonseca R, et al.: Gene Expression Profiling of Myeloma Cells at Diagnosis Can Predict Response to Therapy with Thalidomide and Dexamethasone Combination. ASH Annual Meeting Abstracts 2005, 106(11):508-508.
  • [25]Jeffery IB, Higgins DG, Culhane AC: Comparison and evaluation of methods for generating differentially expressed gene lists from microarray data. BMC Bioinforma 2006, 7:359. BioMed Central Full Text
  • [26]Gupta MK, Qin RY: Mechanism and its regulation of tumor-induced angiogenesis. World J. Gastroentero. 2003, 9(6):1144-1155.
  • [27]Brady-Kalnay SM, Tonks NK: Protein tyrosine phosphatases as adhesion receptors. Curr Opin Cell Biol 1995, 7(5):650-657.
  • [28]Tonks NK: Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 2006, 7(11):833-846.
  • [29]Der SD, Yang Y-L, Weissmann C, Williams BRG: A double-stranded RNA activated protein kinase-dependent pathway mediating stress-induced apoptosis. Proc Natl Acad Sci U S A 1997, 94(7):3279-3283.
  • [30]Markson G, Kiel C, Hyde R, Brown S, Charalabous P, Bremm A, Semple J, Woodsmith J, Duley S, Salehi-Ashtiani K, Vidal M, Komander D, Serrano L, Lehner P, Sanderson CM: Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res 2009, 19(10):1905-11.
  • [31]Inforzato A, Bottazzi B, Garlanda C, Valentino S, Mantovani A: Pentraxins in humoral innate immunity. Adv. Exp. Med. Biol. 2012, 946:1-20.
  • [32]Liu F, Du ZY, He JL, Liu XQ, Yu QB, Wang YX: FTH1 binds to Daxx and inhibits Daxx-mediated cell apoptosis. Mol Biol Rep 2012, 39(2):873-9.
  • [33]Chen CZ, Wang RH, Lee CH, Lin CC, Chang HY, Hsiue TR: Polymorphism of microsomal epoxide hydrolase is associated with chronic obstructive pulmonary disease and bronchodilator response. J. Formos. Med. Assoc. 2011, 110(11):685-9.
  • [34]Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM: Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009, 462(7274):739-44.
  • [35]Noman ASM, Koide N, Hassan F, I-E, Khuda I, Dagvadorj J, Tumurkhuu G, Islam S, Naiki Y, Yoshida T, Yokochi T: Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-α production via down-regulation of MyD88 expression. Innate Immun. 2009, 15(1):33-41.
  • [36]Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP: Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 2002, 30(4):e15.
  • [37]Kerr MK, Martin M, Churchill GA: Analysis of Variance for Gene Expression Microarray Data. J Comput Biol 2000, 7(6):819-837.
  • [38]Hao Wu , Hyuna Yang , Gary A, Churchill : R/MAANOVA. 2009. http://churchill.jax.org/software/rmaanova/maanova.pdf
  • [39]Hong F, Breitling R, McEntee CW, Wittner BS, Nemhauser JL, Chory J: RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 2006, 22(22):2825-2827.
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