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Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors
Authors:Ty W Lebsack  Vuna Fa  Chris C Woods  Raphael Gruener  Ann M Manziello  Michael J Pecaut  Daila S Gridley  Louis S Stodieck  Virginia L Ferguson  Dominick DeLuca
Institution:1. Department of Immunobiology, University of Arizona, Tucson, Arizona 85724;2. Department of Physiology, University of Arizona, Tucson, Arizona 85724;3. Department of Molecular and Cellular Biology, Informatics/Bioinformatics, University of Arizona, Tucson, Arizona 85721;4. Department of Basic Sciences Division of Microbiology and Biochemistry, Loma Linda University, Loma Linda, California 92354;5. Department of Aerospace Engineering, BioServe Space Technologies, University of Colorado, Boulder, Colorado 80309
Abstract:The detrimental effects of spaceflight and simulated microgravity on the immune system have been extensively documented. We report here microarray gene expression analysis, in concert with quantitative RT‐PCR, in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS‐118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age‐ and sex‐matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5‐fold or greater change. When these data were averaged (n = 4), we identified 12 genes that were significantly up‐ or down‐regulated by at least 1.5‐fold after spaceflight (P ≤ 0.05). The genes that significantly differed from the AEM controls and that were also confirmed via QRT‐PCR were as follows: Rbm3 (up‐regulated) and Hsph110, Hsp90aa1, Cxcl10, Stip1, Fkbp4 (down‐regulated). QRT‐PCR confirmed the microarray results and demonstrated additional gene expression alteration in other T cell related genes, including: Ctla‐4, IFN‐α2a (up‐regulated) and CD44 (down‐regulated). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space. J. Cell. Biochem. 110: 372–381, 2010. © 2010 Wiley‐Liss, Inc.
Keywords:thymus  microgravity  spaceflight  gene expression  microarray  T cells  stress
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