Early postnatal, but not late, exposure to chemical ambient pollutant 1,2-naphthoquinone increases susceptibility to pulmonary allergic inflammation at adulthood

Autor(es):Mostrar menos -

Santos, Karen T. ^[1] ; Florenzano, Juliana ^[1] ; Rodrigues, Leandro ^[1] ; Favaro, Rodolfo R. ^[2] ; Ventura, Fernanda F. ^[3] ; Ribeiro, Marcela G. ^[3] ; Teixeira, Simone A. ^[1] ; Ferreira, Heloisa H. A. ^[4] ; Brain, Susan D. ^[5] ; Damazo, Amilcar S. ^[6] ; Zorn, Telma M. ^[2] ; Camara, Niels O. ^[7] ; Muscara, Marcelo N. ^[1] ; Peron, Jean Pierre ^[7] ; Costa, Soraia K. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cellular Biol & Dev, Sao Paulo - Brazil

^[3] Fundacao Jorge Duprat Figueiredo Seguranca & Med, Sao Paulo - Brazil

^[4] Univ Sao Francisco, Inflammat Res Lab, Sao Paulo - Brazil

^[5] Kings Coll London, Pharmaceut Sci Res Div, London WC2R 2LS - England

^[6] Univ Fed Mato Grosso, Fac Med, Dept Basic Sci Hlth, Cuiaba, Mato Grosso - Brazil

^[7] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF TOXICOLOGY; v. 88, n. 8, p. 1589-1605, AUG 2014.
• Citações Web of Science: 4

Resumo

High diesel exhaust particle levels are associated with increased health effects; however, knowledge on the impact of its chemical contaminant 1,2-naphthoquinone (1,2-NQ) is limited. We investigated whether postnatal and adult exposures to 1,2-NQ influence allergic reaction and the roles of innate and adaptive immunity. Male neonate (6 days) and adult (56 days) C57Bl/6 mice were exposed to 1,2-NQ (100 nM; 15 min) for 3 days, and on day 59, they were sensitized and later challenged with ovalbumin (OVA). Airway hyper-responsiveness (AHR) and production of cytokines, immunoglobulin E (IgE) and leukotriene B-4 (LTB4) were measured in the airways. Postnatal exposure to 1,2-NQ activated dendritic cells in splenocytes by increasing expressing cell surface molecules (e.g., CD11c). Co-exposure to OVA effectively polarized T helper (Th) type 2 (Th2) by secreting Th2-mediated cytokines. Re-stimulation with unspecific stimuli (PMA and ionomycin) generated a mixed Th1 (CD4(+)/IFN-gamma(+)) and Th17 (CD4(+)/IL-17(+)) phenotype in comparison with the vehicle-matched group. Postnatal exposure to 1,2-NQ did not induce eosinophilia in the airways at adulthood, although it evoked neutrophilia and exacerbated OVA-induced eosinophilia, Th2 cytokines, IgE and LTB4 production without affecting AHR and mast cell degranulation. At adulthood, 1,2-NQ exposure evoked neutrophilia and increased Th1/Th2 cytokine levels, but failed to affect OVA-induced eosinophilia. In conclusion, postnatal exposure to 1,2-NQ increases the susceptibility to antigen-induced asthma. The mechanism appears to be dependent on increased expression of co-stimulatory molecules, which leads to cell presentation amplification, Th2 polarization and enhanced LTB4, humoral response and Th1/Th2 cytokines. These findings may be useful for future investigations on treatments focused on pulmonary illnesses observed in children living in heavy polluted areas. (AU)

• Processo FAPESP: 09/54826-1 - Efeito da exposicao precoce ao poluente 1,2-nq sobre a resposta imune inata e adquirida em camundongos: papel dos receptores toll
• Beneficiário: Karen Tiago dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/14971-0 - Papel dos receptores Toll nas respostas imunes inata e adquirida de camundongos expostos na fase neonatal ao poluente 1,2-NQ
• Beneficiário: Soraia Katia Pereira Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular