title: TRPA1 mediates the effects of hypothermia on the monocyte inflammatory response.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY. Electronic address: adrianbilleter@bluewin.ch.
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Billeter
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Norman
authors.initials: N
authors.lastname: Galbraith
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Samuel
authors.initials: S
authors.lastname: Walker
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Lawson
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Gardner
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Harshini
authors.initials: H
authors.lastname: Sarojini
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Susan
authors.initials: S
authors.lastname: Galandiuk
authors.affiliation: Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Hiram C
authors.initials: HC
authors.lastname: Polk
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D003080:Cold Temperature / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007035:Hypothermia / Q000276:immunology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D015220:Calcium Channels; D016207:Cytokines; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels