Triclosan (TCS), an antibacterial agent widely found in household and clinical products, is readily absorbed into human skin, but TCS effects on mammalian cells are largely unknown. TCS has been found to alleviate symptoms of human eczema, via an unknown mechanism. Mast cells are ubiquitous, key players in allergy, infectious disease, carcinogenesis, autism, and many other diseases and physiological functions. One important function of mast cells is release of pro-inflammatory mediators from intracellular granules (degranulation) upon challenge with antigen. Non-cytotoxic doses of TCS inhibit several functions of both human (HMC-1.2) and rat (RBL-2H3) mast cells, including degranulation. Previous work in the Gosse laboratory has shown that TCS disrupts ATP production without cytotoxicity in RBL-2H3 and HMC-1.2 mast cells in glucose-free, galactose-containing media. In the same glucose-free conditions, 15 µM TCS dampens RBL-2H3 degranulation by 40%. Thus, TCS affects degranulation and ATP production in mast cells. TCS-methyl, unlike TCS, was shown to inhibit neither of these processes, suggesting that TCS disrupts cellular energy production in part due to its ionizable proton. Well studied mitochondrial uncouplers [e.g., carbonyl cyanide 3-chlorophenylhydrazone (CCCP)] have been shown to disrupt mast cell function.
Oxygen consumption rate (OCR) is a parameter that has been used to study mitochondrial function, since most cellular oxygen consumption is via mitochondria. Triclosan at 10 µM was shown to increase the cellular oxygen consumption rate in RBL-2H3 cells, demonstrating a similar effect as 1 µM CCCP. Taken together, our data indicate that TCS is a mitochondrial uncoupler which disrupts mast cell signaling. This mechanism could underlie TCS toxicity in numerous mammalian cell types.
Hashmi, Hina, "Is the Ubiquitous Antibacterial Agent Triclosan an Uncoupler of Mammalian Mitochondria" (2015). Honors College. 211.