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Is transient receptor potential ankyrin 1 (TRPA1) signaling required for innate immunity against increased asthma susceptibility due to early air pollutant contact?

Pesquisador responsável:

Soraia Katia Pereira Costa

Beneficiário:

Instituição: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo, SP, Brasil
Pesquisador responsável no exterior: Susan Diane Brain
Instituição no exterior: King's College London. (Reino Unido)
Área do conhecimento:Ciências Biológicas - Farmacologia - Toxicologia
Linha de fomento:Auxílio à Pesquisa - Regular
Processo: 12/50589-8
Vigência: 01 de outubro de 2012 - 31 de dezembro de 2014
Convênio/Acordo de cooperação com a FAPESP: King's College London
Assunto(s):

Poluentes ambientais

Asma

Receptores purinérgicos P1

Canais de cálcio

Receptores toll-like

Naftoquinonas

Estresse oxidativo

Resumo
The impact of air pollution on population health, mainly on the prevalence of asthma and cardiovascular diseases, has been shown in several epidemiological studies but only in few pharmacological reports. The nonselective transient receptor potential cation channel TRPA1 is a specific target for electrophilic chemical components of Diesel Exhaust Particles (PED), thus its activation represents an important mechanism for DEP pneumotoxicity. We showed that DEP-induced airways inflammation is highly influenced by increased concentration of 1,2-naphthoquinone (1,2-NQ), and takes place by neurogenic mechanisms involving up-regulation of TRPV1. Moreover, the exposure of neonate mice to 1,2-NQ enhances susceptibility to allergic inflammation at adulthood, via mechanism dependent on interaction with primary innate immune toll-like 4 receptors and reduced lung antioxidant defenses. Oxidizing agents and lipid peroxidation products released by air pollutants activate TRPA1 channels in bronchopulmonary C-fibres terminals, leading to central reflexes (cough) and neurogenic inflammation. Whether C fibres activation occurs by, direct or indirect, interaction of oxidizing agents formed by 1,2-NQ with TRPA1 channels is unknown. We aimed to investigate the role of TRPA1 and its possible interaction with 1,2-NQ-induced TLR-mediated changes in targets of the innate immune function, that exert a positive regulatory effect on Th downstream genes / pathways signalling. (AU)

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