Introduction
Hypothermia is a well-known risk factor for postoperative complications because it
prolongs the monocyte inflammatory response. The purpose of this study was to investigate
whether temperature-activated ion channels (transient receptor protein channels [TRP]
A1 and V1) mediate the effects of temperature on monocytes.
Methods
Primary human monocytes were isolated and stimulated with lipopolysaccharide at 32°C
or 39°C. RNA was isolated for analysis of microRNA (miR)-155 expression, and cytokines
in the supernatant were measured with an enzyme-linked immunosorbent assay. Specific
inhibitors of TRPA1 (HC- 030031) and a specific activator of TRPV1 (capsaicin) were
used to block or activate TRPA1 and TRPV1, respectively. Statistical analysis was
performed using the Wilcoxon signed-rank test.
Results
TRPM8 mRNA was not expressed in primary human monocytes, whereas TRPA1 and TRPV1 were
expressed. TRPV1 mRNA expression was suppressed at 32°C but not at 39°C. TRPA1 was
induced strongly at 32°C and 39°C. Immunofluorescence microscopy confirmed that monocytes
express TRPA1 and TRPV1 on their cell surface. Interleukin-10 secretion was increased
by blocking TRPA1 (77.8 ± 3 2.8 pg/mL) and activating TRPA1 (79.4 ± 16.1 pg/mL) after
24 hours at 32°C (control 37.4 ± 17.1 pg/mL, P < .05). At 36 hours, tumor necrosis factor secretion was decreased after TRPA1 blockade
(2,321 ± 439 pg/mL) and TRPV1 activation (2,137 ± 411 pg/mL) compared with control
(2,567 ± 495 pg/mL, P < .05). Furthermore, miR-155 expression also was suppressed at 24 hours by TRPA1
blockade and TRPV1 activation (both P < .05). Silencing of TRPA1 normalized monocyte IL-10 secretion at 32°C.
Conclusion
These results demonstrate that hypothermia mediates its effects on monocytes through
TRPA1. Blockade of TRPA1 or activation of TRPV1 may be used to modify the effects
of hypothermia on the monocyte inflammatory response.
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Article info
Publication history
Published online: June 05, 2015
Accepted:
March 12,
2015
Footnotes
This work was funded by the Price Trust Fund, by the Joint Royal College of Surgeons of Edinburgh (RCSEd)/James and Emmeline Ferguson Research Fellowship Trust. Dr Billeter holds the Joint Royal College of Surgeons of Edinburgh (RCSEd)/James and Emmeline Ferguson Research Fellowship. The funding sources did not have any influence on the production of the manuscript.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
