Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study

Area of Science:

• Cellular and Molecular Biology
• Physiology
• Immunology

Background:

• The precise cellular mechanisms of moderate hypothermia (32°C for 12-72 hours) on human cell function remain largely unknown.
• Understanding these effects is crucial for applications involving therapeutic hypothermia or accidental cold exposure.

Purpose of the Study:

• To investigate the hypothesis that moderate hypothermia induces widespread changes in messenger RNA (mRNA) expression in human cells in vitro.
• To identify specific genes and functional pathways affected by hypothermic conditions.

Main Methods:

• Human acute monocytic leukemia (THP-1) cells were exposed to moderate hypothermia (32°C) or control conditions (37°C) for 24 hours.
• Gene expression profiling was conducted using Affymetrix U133A chips on seven paired samples.
• Statistical methods identified significant changes in mRNA expression, with a fold-change threshold of ≥2 and specific call criteria.

Main Results:

• Moderate hypothermia resulted in 67 sequences with increased mRNA expression, including cold-inducible genes like CIRBP and RNA binding motif 3.
• 100 sequences exhibited decreased mRNA expression.
• Affected functional categories included immune responses, cell growth, proliferation, differentiation, metabolism, and biosynthesis. Several heat shock proteins (HSPs) showed reduced expression.

Conclusions:

• Moderate hypothermia induces substantial and broad changes in cellular gene expression.
• These alterations impact key cellular functions, including immune response and metabolism.
• The findings suggest that prolonged hypothermia in vivo could lead to physiologically relevant changes in circulating leukocytes.