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Early postnatal,but not late,exposure to chemical ambient pollutant 1,2-naphthoquinone increases susceptibility to pulmonary allergic inflammation at adulthood
Authors:Karen T. Santos  Juliana Florenzano  Leandro Rodrigues  Rodolfo R. Fávaro  Fernanda F. Ventura  Marcela G. Ribeiro  Simone A. Teixeira  Heloisa H. A. Ferreira  Susan D. Brain  Amílcar S. Damazo  Telma M. Zorn  Niels O. Câmara  Marcelo N. Muscará  Jean Pierre Peron  Soraia K. Costa
Affiliation:1. Department of Pharmacology, Institute of Biomedical Sciences, University of S?o Paulo, Av Prof Lineu Prestes, 1524, S?o Paulo, SP, 05508-900, Brazil
2. Department of Cellular Biology and Development, Institute of Biomedical Sciences, University of S?o Paulo, S?o Paulo, Brazil
4. Funda??o Jorge Duprat Figueiredo de Seguran?a e Medicina do Trabalho, S?o Paulo, Brazil
5. Laboratory of Inflammation Research, S?o Francisco University, Bragan?a Paulista, S?o Paulo, Brazil
6. Pharmaceutical Science Research Division, Franklin–Wilkins Building, King’s College, London, UK
7. Department of Basic Science in Health, Faculty of Medicine, Federal University of Mato Grosso, Mato Grosso, Brazil
3. Department of Immunology, Institute of Biomedical Sciences, University of S?o Paulo, S?o Paulo, Brazil
Abstract: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 B4 (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-γ+) 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.
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