Role of Toll-like receptor in mediating both immune innate and adaptive responses to ambient pollutant 1,2-NQ in neonatal mice

• Grant number: 10/14971-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2010
• End date: May 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Soraia Katia Pereira Costa
• Grantee: Soraia Katia Pereira Costa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Marcelo Nicolas Muscara
• Associated research grant(s): 12/50589-8 - Is transient receptor potential ankyrin 1 (TRPA1) signaling required for innate immunity against increased asthma susceptibility due to early air pollutant contact?, AP.R

Abstract

Several studies have reported a significant relationship between cigarette smoking and cardiovascular impairment of susceptible individuals, e.g. infants and elderly people; but, there is limited literature that assesses the role of diesel exhaust particles (DEP) and its contaminant 1,2-naphthoquinone (1,2-NQ) in postnatal follow-up. Interestingly, exposure to DEP increases gene expression of toll like-receptors TLR2 e TLR4 in the lung of mice. Moreover, chemicals such as imidazoquinoline and loxoribine seem to act as ligants of TLR7 and 8. Recently, we attempted to model the environment of a child born in a polluted metropolitan area, in which DEP contaminant, 1.2-naphthoquinone (1.2-NQ), is one of the major contributors, and found that neonatal exposure to this chemical increased susceptibility of mice to asthma at an adult stage. The involved mechanisms are not fully established, although we hypothesized that these effects might be the result of increased expression and / or activity of the innate response factors in exposed animals This in turn can affect the their immune system homeostasis and thus impairs the balance of Th1/Th2 immune response. We will now further this study in order to investigate the mechanisms possibly involved in the deterioration of asthma features by early exposure of mice to 1.2-NQ. To reach this, we propose to carry out comparative studies (in vivo and in vitro) in wild type, TLR4-mutant and both TLR4- and myeloid differentiation primary-response protein 88 (MyD88)-knockout mice. The functional and biochemical assays established in our laboratory are Penh, gene (via qRT-PCR) and protein expression (via Western boot) of TLR4, TLR7, IL-1R, IL-4R, related molecules and transcription factors. Surface molecules and lymphocytic population will be measured via flow citometry. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS, KAREN T.; FLORENZANO, JULIANA; RODRIGUES, LEANDRO; FAVARO, RODOLFO R.; VENTURA, FERNANDA F.; RIBEIRO, MARCELA G.; TEIXEIRA, SIMONE A.; FERREIRA, HELOISA H. A.; BRAIN, SUSAN D.; DAMAZO, AMILCAR S.; et al. Early postnatal, but not late, exposure to chemical ambient pollutant 1,2-naphthoquinone increases susceptibility to pulmonary allergic inflammation at adulthood. ARCHIVES OF TOXICOLOGY, v. 88, n. 8, p. 1589-1605, AUG 2014. (10/14971-0)