Adjuvant Effect of an Alternative Plasticizer, Diisopropyl Adipate, on a Contact Hypersensitivity Mouse Model: Link with Sensory Ion Channel TRPA1 Activation.

Due to health concerns about phthalate esters, the use of alternative plasticizers is being considered. Phthalate esters enhance skin sensitization to fluorescein isothiocyanate (FITC) in mouse models. We have demonstrated that phthalate esters stimulate transient receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory neurons. We also found a correlation between TRPA1 activation and the enhancing effect on FITC-induced contact hypersensitivity (CHS) when testing various types of phthalate esters. Here we investigated the effects of an alternative plasticizer, diisopropyl adipate (DIA). Activation of TRPA1 by DIA was demonstrated by calcium mobilization using Chinese hamster ovary cells expressing TRPA1 in vitro. The effect of DIA was inhibited by a TRPA1-specific antagonist, HC-030031. The presence of DIA or dibutyl phthalate (DBP; positive control) during skin sensitization of BALB/c mice to FITC augmented the CHS response, as revealed by the level of ear-swelling. The enhancing effect of DIA was inhibited by in vivo pretreatment with HC-030031. FITC-presenting CD11c(+) dendritic cell (DC)-trafficking to draining lymph nodes was facilitated both by DIA and by DBP. DBP and DIA were similarly active in the enhancement of interferon-γ production by draining lymph nodes, but the effect on interleukin-4 production was weaker with DIA. Overall, DIA activated TRPA1 and enhanced FITC-induced CHS, as DBP did. The adjuvant effects of adipate esters may need to be considered because they are used as ingredients in cosmetics and drug formulations topically applied to the skin.

TRPV1-mediated itch in seasonal allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). AIM OF THE STUDY: To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. METHODS: Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season. RESULTS: The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea. CONCLUSION: Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition.