Abstract
Phthalates, such as bis(2-ethylhexyl) phthalate (DEHP), are extensively used as a plasticizer in consumer products, and are almost ubiquitous pollutants in indoor air and house dust. Recent several studies have revealed that transient receptor potential (TRP) A1, a sensory neuronal TRP ion channel, plays an essential role in chemosensation and inflammation in airway, skin and eye together with TRPV1, the capsaicin receptor. It has been demonstrated that these ion channels are activated by various chemicals, including formaldehyde, acrolein and cigarette smoke, which are thought to be contributing factors in sick building syndrome. In this study, we examined the activation of TRP channels, TRPV1 and TRPA1, by phthalates and its hydrolysis products.
We established Flp-In 293 cell lines stably expressing either human TRPV1 or human TRPA1 ion channels. To demonstrate the activation of TRP channels, calcium influx in cells was measured by FLIPR Calcium assay 5 kit and Flexstation (Molecular devices).
We found that diethyl phthalate, di-n-octyl phthate, monobutyl phthalate, monobenzyl phthalate, monoethylhexyl phthalate and 2-ethyl-1-hexanol activated hTRPV1 and/or hTRPA1. We have reported that monobutyl phthalate and monoethylhexyl phthalate were detected in house dust. It has been reported that 2-ethyl-1-hexanol was detected in indoor air and suggested to associate with sick building syndrome. These results suggest that these phthalates and its hydrolysis products may cause sensory nerve activation and sensory irritation of airway, skin and eye via the activation of TRPV1 and TRPA1. Our data may also help elucidate the mechanisms underlying indoor environment-related symptoms such as sick building syndrome and so-called “multiple chemical sensitivity syndrome”.
