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E-GEOD-4425 - Transcription profiling of human actute monocytic leukemia cell line THP-1 cells incubated at 37 or 32 degrees C for 24h reveals moderate hypothermia produces substantial changes in cellular gene expression, in categories potentially of importance to systemic function
Submitted on 8 March 2006, released on 26 October 2007, last updated on 27 March 2012
Background: Moderate hypothermia (32oC for 12 – 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA. Methods: Acute monocytic leukemia THP-1 cells were incubated under control conditions (37oC) or moderate hypothermia (32oC) for 24 hours. Cellular mRNA was extracted and a cold stress response was confirmed by examining the expression of the cold-inducible gene CIRBP by reverse transcription PCR (RT-PCR). Gene expression analysis was performed on seven sets of samples with Affymetrix U133A chips, using established statistical methods. Sequences were considered to be affected by cold if they showed statistically significant changes in expression and also met published post-hoc filter criteria (changes in geometric mean expression of 2-fold or greater and detection calls of “present” or “marginal” in at least half of the experiments). The changes in expression of a select number of these sequences were further confirmed by PCR. Results: 167 sequences met our prospectively defined criteria for a change in expression; 67 showed increases in expression and 100 showed decreases in expression. Consistent with prior literature, the cold-inducible genes CIRBP and RBM3 showed increases in expression. Functional categories affected by cold stress included genes involved in immune responses, cell growth, proliferation, and differentiation, and metabolism and biosynthesis. Several heat shock proteins (HSPs) showed decreases in expression. Conclusions: Moderate hypothermia produces substantial changes in cellular gene expression, in categories potentially of importance to systemic function. Interestingly, cold exposure without re-warming decreased the expression of several HSPs. Our in vitro findings suggest that moderate hypothermia in vivo might produce physiologically important changes in gene expression by circulating leukocytes. Experiment Overall Design: Seven sets of paired THP-1 samples, grown under either control (37oC) or hypothermic (32oC) conditions for 24 hours
transcription profiling by array, co-expression, in vitro, stimulus or stress
Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study. Larry A Sonna, Matthew M Kuhlmeier, Heather C Carter, Jeffrey D Hasday, Craig M Lilly, Karen D Fairchild. Physiol Genomics 26(1):91-8 (2006)