Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors.
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 < or = 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-alpha2a (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.
Lebsack
Ty W
TW
Department of Immunobiology, University of Arizona, Tucson, Arizona 85724, USA. lebsack@email.arizona.edu
Fa
Vuna
V
Woods
Chris C
CC
Gruener
Raphael
R
Manziello
Ann M
AM
Pecaut
Michael J
MJ
Gridley
Daila S
DS
Stodieck
Louis S
LS
Ferguson
Virginia L
VL
Deluca
Dominick
D
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013026:Space Flight; D013312:Stress, Physiological; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014893:Weightlessness
D017931:DNA Primers; D011965:Receptors, Glucocorticoid