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- W1928931434 abstract "Chemosensory Transient Receptor Potential (TRP) channels on airway sensory nerves are potential targets for the treatment of chemical-induced respiratory pathologies. Therefore, we examined the role of TRPA1 and TRPV1 in a mouse model of allergic chemical-induced airway hyperresponsiveness (AHR). On days 1 and 8, wild type (WT) C57Bl/6 mice were dermally treated with 1% toluene-2,4-diisocyanate (TDI) or vehicle (acetone/olive oil). On day 15, mice received a single intranasal challenge with 0.1% TDI or vehicle. In a first set-up, these mice received an IP injection of the NK1R antagonist RP67580 , prior to the challenge. In a second set-up, the TDI challenge was replaced by a TRPA1 or TRPV1 agonist challenge. We performed in vitro intracellular calcium imaging experiments using Chinese Hamster Ovarian (CHO) cells, selectively expressing mTRPA1 or mTRPV1. A challenge with TDI evoked a 50% decrease in respiratory frequency immediately after the intranasal challenge, indicative for sensory irritation. One day later, TDI-sensitized and challenged mice showed AHR, without signs of lung inflammation. TDI-treated mice, injected with the NK1R antagonist did not develop AHR, compared to vehicle-injected mice. Replacing the TDI challenge with a specific TRPA1 or TRPV1 agonist did also not induce AHR in TDI-treated mice. The in vitro experiment showed that 0.001% TDI induced an increased calcium influx in mTRPA1-, but not TRPV1-expressing CHO cells. These results indicate an important role for TRP channels in our mouse model. Yet, merely activating TRP channels in the challenge phase is not sufficient to induce AHR, indicating the importance of the allergen-specific challenge." @default.
- W1928931434 created "2016-06-24" @default.
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- W1928931434 date "2014-09-01" @default.
- W1928931434 modified "2023-10-17" @default.
- W1928931434 title "Transient receptor potential channels in a mouse model of isocyanate-induced airway hyperresponsiveness" @default.
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