TRPA1 mediates the effects of hypothermia on the monocyte inflammatory response

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 degrees C or 39 degrees 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 degrees C but not at 39 degrees C. TRPA1 was induced strongly at 32 degrees C and 39 degrees 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 degrees 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 degrees 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.