The cation channel TRPM8 influences the differentiation and function of human monocytes

Abstract

Monocytes are mononuclear phagocytes that can differentiate to a variety of cell fates under the influence of their microenvironment and hardwired commitment. We found that inhibition of TRPM8 in human blood CD14+ monocytes during a critical 3‐h window at the beginning of their differentiation into macrophages led to enhanced survival and LPS‐driven TNFα production after 24 h. TRPM8 antagonism also promoted LPS‐driven TNFα production in CD14+ monocytes derived from the intestinal mucosa. Macrophages that had been derived for 6 days under blockade of TRPM8 had impaired phagocytic capacity and were transcriptionally distinct. Most of the affected genes were altered in a way that opposed normal monocyte to macrophage differentiation indicating that TRPM8 activity promotes aspects of this differentiation programme. Thus, we reveal a novel role for TRPM8 in regulating human CD14+ monocyte fate and function.

Cold sensor, hot topic: TRPM8 plays a role in monocyte function and differentiation

“…These findings are explored in line with gene expression and RNA analysis. Ultimately the group determines that 253 genes and 331 genes in the AMTB challenge group are up‐regulated and down‐regulated when compared to genes expressed during typical Mϕ differentiation, respectively 3 . These findings further demonstrate that engagement of this channel is crucial for gene transcription that ultimately leads to differentiation of Mϕs from bone marrow‐derived monocytes.…”

“…Other promising areas for future study include exactly how depolarization of the membrane occurs, whether it be inhibition of endosomal channels leading to calcium accumulation in the cell cytoplasm, or if other cation channels are activated as a compensatory mechanism 3 . Finally, potential roles for T cell differentiation and inflammatory cytokine release are also uncovered during this study with respect to activation and inhibition of the TRPM8 channel.…”

“…further explores the role of TRPM8 in human monocyte differentiation and Mϕ participation in the development of colitis in human patients. Hornsby et al 3 . show that inhibition of the TRPM8 channel with a known antagonist, N ‐(3‐aminopropyl)−2‐{[(3‐methylphenyl) methyl]oxy}‐ N ‐(2‐thienylmethyl)benzamide hydrochloride salt (AMTB), leads to plasma membrane depolarization of CD14 + monocytes and monocyte‐derived Mϕs 3 .…”

“…1 Conversely, bone marrow-derived dendritic cells cultured from the 2 groups did not consistently exhibit increased release of IL-6 and IL-1β. 1 In the current issue of the Journal of Leukocyte Biology, Hornsby et al 3 further explores the role of TRPM8 in human monocyte differentiation and Mϕ participation in the development of colitis in human patients. Hornsby et al 3 show that inhibition of the TRPM8 channel with a known antagonist,…”

“…1 In the current issue of the Journal of Leukocyte Biology, Hornsby et al 3 further explores the role of TRPM8 in human monocyte differentiation and Mϕ participation in the development of colitis in human patients. Hornsby et al 3 show that inhibition of the TRPM8 channel with a known antagonist,…”