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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-sede da pesquisa: 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, Inglaterra
    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
    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
    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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