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01 November 2005

Comment to: Regulation of various genes in human leukocytes acutely exposed to morphine: expression microarray analysis.

Shigemasa Sawada

Med Sci Monit 2005; 11(11): LE19-20 :: ID: 430403


Dear Editor, I was intrigued by the recent article entitled "Regulationof various genes in human leukocytes acutely exposed to morphine: expression microarray analysis" byStefano et al. [1] The study demonstrated that acute chemical (morphine) exposure resulted in a multitudeof specific gene expressions, and indicated that morphine tends to downregulate proinflammatory geneexpression, i.e., TNF signaling pathway, early growth response 1, interleukin 1-beta, chemokine, CXCMotif, Kigand1 (CXCL3), etc, and to upregulate genes associated with signal transducers and activatorsof transcription5A (STAT5A), interferon gamma (IFN-gamma), mitogen-activated protein kinase 2 (MAP2k2)and interleukin 10 receptor beta, etc. The study supports the notion that endogenous morphine activatesselect signaling cascades and that it downregulates tissue excitation and also that a single moleculelike morphine is able to affect numerous systems and to influence immune and inflammation phenomena.It reminded us that this kind of study is due to the development of DNA technology and advanced recentcomputed technology. It has been waited impatiently to know the roles of molecules in various disorders,particularly the fates of molecules within the cells The modern techniques, such as gene expression analysis,gene targeting and single cell cultivation, allow us to explore the etiopathogenesis of various diseasesat the molecular level. Gene expression analysis, particularly DNA chips, has attracted tremendous interestamong medical scientists and biologists due to its potential for providing new perspectives on previouslyunknown biological phenomena. The following methods have recently been established and applied to basicand clinical studies: differential display [2]; suppression subtractive hybridization [3]; cDNA microarrayhybridization [4]; and serial analysis of gene expression (SAGE) [5]. Microarray systems are powerfultools for analyzing the expression profiles of thousands of genes in a wide range of biological systems.Microarray analysis has recently been applied to research into various clinical disorders, such as lymphoma,Huntington's disease and myocardial infarction, and disease-related genes have been isolated for someof these disorders [6-10]. Sjögren's syndrome (SS) is an autoimmune disease characterized by the massiveinfiltration of lymphocytes into exocrine glands, such as salivary and lacrimal glands, and the subsequentdestruction of these exocrine glands. Like other autoimmune diseases, the etiology of SS remains unclear.We have isolated genes that contribute to the progression of SS using mRNA from a mouse model of SS (MRL/lprand NFS/sld) and an in-house cDNA microarray. In this model, we identified a number of up-regulated genes.Fifteen highly expressed genes (IL-16, Grap, caspase3, Ly-6C.2, Mel-14 antigen, cathepsin B, mpt1, Laptm5,Gnai2, vimentin, UCP2, saposin, Trt, laminin receptor 1, and HSP 70 cognate) were identified in the salivaryglands of MRL/lpr mice by cDNA microarray analysis. Expression of 9 of these genes (IL-16, Grap, caspase3,Ly6c2, Mel-14 antigen, cathepsinB, mpt1 Laptm5, and Gnai2) was higher in the salivary glands of thymectomized-NFS/sldmice than in control mice that did not undergo thymectomy. Furthermore, 5 genes (mpt1, Laptm5, UCP2,Gnai2 and IL16) had not been previously identified as SS-related genes [11]. Unfortunately, it is notyet clear why these genes are spontaneously up-regulated in sick mice. Since the technology was developed,many successful microarray studies have been reported. Advances in computational and microarray technologycontinue to open new avenues of biological investigation. However, we must continue to heed Bednar'swarning regarding the negative implications of the DNA microarray technology; who will ensure that suchdata is not misused or required as a part of a job interview? Will such knowledge influence people'schoices of a partner/spouse or lead to the artificial selection of human embryos? Although the arrivalof DNA microarray technology itself brings about new scientific world to us, the abuse of the technologymust be prevented [12]. Sincerely, Shigemasa Sawada, Professor of Medicine, Division of Rheumatologyand Hematology, Nihon University Nerima Hikarigaoka Hospital, Tokyo, Japan, e-mail: [email protected]: [1]Stefano GB, Burrill JD, Labur S et al: Regulation of various genes in human leukocytesacutely exposed to morphine: expression microarray analysis. Med Sci Monit, 2005;11(5): MS35-MS42 [2]LiangP, Pardee AB: Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.Science, 1992; 257: 967-71 [3]Diatchenko L, Lau YF, Campbell AP et al: Suppression subtractive hybridization:A method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc NatlAcad Sci USA, 1996; 93: 6025-30 [4]Schena M, Shalon D, Davis RW, Brown PO: Quantitative monitoring ofgene expression patterns with a complementary DNA microarray. Science, 1995; 270: 467-70 [5]VelculescuVE, Zhang L, Vogelstein B, Kinzler KW: Serial analysis of gene expression. Science, 1995; 270: 484-87[6]Brown PO, Botstein D: Exploring the new world of the genome with DNA microarrays. Nat Genet, 1999;21: 33-37 [7]Yoshikawa T, Nagasugi Y, Azuma T et al: Isolation of Novel Mouse Genes Differentially Expressedin Brain Using cDNA Microarray. Biochem Biophys Res Commun, 2000; 275: 532-37 [8]Alizadeh AA, Eisen MB,Davis RE et al: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.Nature, 2000; 403: 503-11 [9]Luthi-Carter R, Strand A, Peters NL et al: Decreased expression of striatalsignaling genes in a mouse model of Huntington's disease. Hum Mol Genet, 2000; 9: 1259-71 [10]StantonLW, Garrard LJ, Damm D et al: Altered patterns of gene expression in response to myocardial infarction.Circ Res, 2000; 86: 939-45 [11]Takei M, Shiraiwa H, Azuma T et al: The possible etiopathogenic genesof Sjogren's syndrome. Autoimmunity Reviews, 2005; 4(7): 479-84 [12]Bednar M: DNA microarray technologyand application. Med Sci Monit, 2000; 6(4): 796-800.

Keywords: Gene Expression Regulation, Leukocytes - metabolism, Morphine - pharmacology, Oligonucleotide Array Sequence Analysis

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Medical Science Monitor eISSN: 1643-3750