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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?

Processo: 12/50589-8
Modalidade de apoio:Auxílio à Pesquisa - Regular
Vigência: 01 de outubro de 2012 - 31 de dezembro de 2014
Área do conhecimento:Ciências Biológicas - Farmacologia - Toxicologia
Convênio/Acordo: King's College London
Pesquisador responsável:Soraia Katia Pereira Costa
Beneficiário:Soraia Katia Pereira Costa
Pesq. responsável no exterior: Susan Diane Brain
Instituição no exterior: King's College London, Inglaterra
Instituição Sede: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brasil
Vinculado ao auxílio:10/14971-0 - Papel dos receptores Toll nas respostas imunes inata e adquirida de camundongos expostos na fase neonatal ao poluente 1,2-NQ, AP.R
Assunto(s):Poluentes ambientais  Asma  Receptores purinérgicos P1  Canais de cálcio  Receptores toll-like  Naftoquinonas  Estresse oxidativo 
Palavra(s)-Chave do Pesquisador:Asthma | Environmental Pollutants | Oxidative Stress | Toll Like Receptors | Trpa1 Channels | 1 2 Naphthoquinone


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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