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
• Data de Início da vigência: 01 de outubro de 2012
• Data de Término da vigência: 31 de dezembro de 2014
• Área do conhecimento: Ciências Biológicas - Farmacologia - Toxicologia
• Acordo de Cooperação: King's College London
• Pesquisador responsável: Soraia Katia Pereira Costa
• Beneficiário: Soraia Katia Pereira Costa
• Pesquisador Responsável no exterior: Susan Diane Brain
• Instituição Parceira 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

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)