Journal of Applied Physiology
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J Appl Physiol (January 11, 2002). doi:10.1152/japplphysiol.01002.2001
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Articles in PresS, published online ahead of print January 11, 2002
J Appl Physiol, 10.1152/jap.01002.2001
Submitted on October 1, 2001
Accepted on January 4, 2002

The Effect of Acute Heat Shock on Gene Expression by Human Peripheral Blood Mononuclear Cells

Larry A Sonna1*, Stephen L Gaffin2, Richard E Pratt3, Michael L Cullivan2, Karen C Angel2, and Craig M Lilly4

1 Thermal and Mountain Medicine Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital / Harvard Medical School, Boston, MA, USA
2 Thermal and Mountain Medicine Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA
3 Partners Gene Array Technology Center, Brigham and Women's Hospital / Harvard Medical School, Boston, MA, USA
4 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital / Harvard Medical School, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: larry.sonna{at}na.amedd.army.mil, LSONNA@NATICK-CCMAIL.ARMY.MIL.

We studied the effect of heat shock on gene expression by normal human cells. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy adults. Paired samples from each subject were subjected to either 20 minutes of heat shock (43°C) or control (37°C) conditions, then returned to 37°C. RNA was isolated 160 minutes later and five representative samples were analyzed on Affymetrix gene chip arrays containing ~12,600 probes. A biologically meaningful effect was defined as a statistically significant, 2-fold or greater difference in expression of sequences that were detected in all 5 experiments under control (downregulated sequences) or heat shock (upregulated sequences) conditions. Changes occurred in 420 sequences (239 increased by heat shock, 181 decreased) representing 376 Unigene numbers, in every functional category previously implicated in the heat shock response. By RT-PCR, we confirmed the findings for one upregulated gene (Rad, a G-protein) and one downregulated gene (osteopontin, a cytokine). We conclude that heat shock causes extensive gene expression changes in PBMCs, affecting all functional categories of the heat shock response.




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