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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?

Grant number: 12/50589-8
Support type:Regular Research Grants
Duration: October 01, 2012 - December 31, 2014
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Cooperation agreement: King's College London
Principal researcher:Soraia Katia Pereira Costa
Grantee:Soraia Katia Pereira Costa
Principal researcher abroad: Susan Diane Brain
Institution abroad: King's College London, England
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:10/14971-0 - Role of Toll-like receptor in mediating both immune innate and adaptive responses to ambient pollutant 1,2-NQ in neonatal mice, AP.R

Abstract

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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