Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes

Triclosan (TCS) is an antimicrobial used widely in hospitals and personal care products, at similar to 10mm. Human skin efficiently absorbs TCS. Mast cells are ubiquitous key players both in physiological processes and in disease, including asthma, cancer and autism. We previously showed that non-cytotoxic levels of TCS inhibit degranulation, the release of histamine and other mediators, from rat basophilic leukemia mast cells (RBL-2H3), and in this study, we replicate this finding in human mast cells (HMC-1.2). Our investigation into the molecular mechanisms underlying this effect led to the discovery that TCS disrupts adenosine triphosphate (ATP) production in RBL-2H3 cells in glucose-free, galactose-containing media (95% confidence interval EC50 = 7.5-9.7 mu m), without causing cytotoxicity. Using these same glucose-free conditions, 15 mu m TCS dampens RBL-2H3 degranulation by 40%. The same ATP disruption was found with human HMC-1.2 cells (EC50 4.2-13.7 mu m), NIH-3T3 mouse fibroblasts (EC50 4.8-7.4 mu m) and primary human keratinocytes (EC50 3.0-4.1 mu m) all with no cytotoxicity. TCS increases oxygen consumption rate in RBL-2H3 cells. Known mitochondrial uncouplers (e.g., carbonyl cyanide 3-chlorophenylhydrazone) previously were found to inhibit mast cell function. TCS-methyl, which has a methyl group in place of the TCS ionizable proton, affects neither degranulation nor ATP production at non-cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its proton ionophore structure. In addition, 5 mu m TCS inhibits thapsigargin-stimulated degranulation of RBL-2H3 cells: further evidence that TCS disrupts mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and TCS may affect numerous cell types and functions via this mechanism. Copyright (c) 2015 John Wiley & Sons, Ltd. Triclosan (TCS) is an antimicrobial agent and mast cells are ubiquitous players in physiological processes and in diseases. TCS disrupts adenosine triphosphate production in mast cells, mouse fibroblasts and primary human keratinocytes and increases the oxygen consumption rate. TCS-methyl (no ionizable proton) affects neither degranulation nor adenosine triphosphate production at non-cytotoxic doses, indicating the effects of TCS are due to its proton ionophore structure. TCS is a mitochondrial uncoupler, affecting numerous cell types and functions via this mechanism.