Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-16T11:49:50Z No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-16T11:59:43Z (GMT) No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5)Made available in DSpace on 2018-08-16T11:59:43Z (GMT). No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5) Previous issue date: 2018Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB).Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Allergy and Acarology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilAtopic asthma, which is characterized by the chronic inflammation and morbidity of airways, is a disease of great complexity, and multiple genetic and environmental factors are involved in its etiology. In the first genome-wide association study (GWAS) conducted in Brazil for asthma, a positive association was found between atopic asthma and a variant (rs1999071), which is located between the DAD1 and OXA1L genes, although neither gene has previously been reported to be associated with asthma or allergies. The DAD1 gene is involved in the regulation of programmed cell death, and OXA1L is involved in biogenesis and mitochondrial oxidative phosphorylation. This study aimed to evaluate how polymorphisms in DAD1 and OXA1L are associated with asthma and markers of atopy in individuals from the Salvador cohort of the SCAALA (Social Change Asthma and Allergy in Latin America) program. The DNA of 1220 individuals was genotyped using the Illumina 2.5 Human Omni Bead chip. Logistic regression analyses were performed with PLINK 1.9 software to verify the association between DAD1 and OXA1L polymorphisms and asthma and atopic markers, adjusted for sex, age, helminth infections and ancestry markers, using an additive model. The DAD1 and OXA1L genes were associated with some of the evaluated phenotypes, such as asthma, skin prick test (SPT), specific IgE for aeroallergens, and Th1/Th2-type cytokine production. Using qPCR, as well as in silico gene expression analysis, we have demonstrated that some of the polymorphisms in both genes are able to affect their respective gene expression levels. In addition, DAD1 was over-expressed in asthmatic patients when compared with controls. Thus, our findings demonstrate that variants in both the DAD1 and OXA1L genes may affect atopy and asthma in a Latin American population with a high prevalence of asthma

The anti-allergic activity of Cymbopogon citratus is mediated via inhibition of nuclear factor kappa B (Nf-Κb) activation.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-04-15T17:07:01Z No. of bitstreams: 1 Machado MSS The anti-allergic....pdf: 3177342 bytes, checksum: 00bb337c0a5ed554f118913bc51a2219 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-04-15T17:26:57Z (GMT) No. of bitstreams: 1 Machado MSS The anti-allergic....pdf: 3177342 bytes, checksum: 00bb337c0a5ed554f118913bc51a2219 (MD5)Made available in DSpace on 2016-04-15T17:26:57Z (GMT). No. of bitstreams: 1 Machado MSS The anti-allergic....pdf: 3177342 bytes, checksum: 00bb337c0a5ed554f118913bc51a2219 (MD5) Previous issue date: 2015Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, Brasil / Faculdade Adventista da Bahia. Cachoeira, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilFaculdade Adventista da Bahia. Cachoeira, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilFaculdade Adventista da Bahia. Cachoeira, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Biologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Ba, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biorregulação. Salvador, BA, BrasilBACKGROUND: The prevalence of allergic diseases such as asthma has significantly increased worldwide, making it a public health concern. There is an urgent need for new anti-inflammatory agents with selective pharmacology and lower toxicity. Plant extracts have been used for centuries in traditional medicine to alleviate inflammatory diseases. In this work, we evaluated the anti-allergic activity of Cymbopogon citratus (Cy), a medicinal herb used by folk medicine to treat asthma. METHODS: We used a murine model of respiratory allergy to the mite Blomia tropicalis (Bt) and evaluated certain parameters known to be altered in this model. A/J mice were sensitized (100 µg/animal s.c.) and challenged (10 µg/animal i.n.) with Bt mite extract and treated with 60, 120 or 180 mg/kg of Cy standardized hexane extract. The parameters evaluated included: cellular infiltrate in bronchoalveolar lavage (BAL); eosinophil peroxidase activity (EPO); histopathological examination of the lung; serum levels of specific IgE, IgG1 and IgG2a; Th2 cytokine concentrations in BAL and expression of NF-κB. RESULTS: Our results showed that oral administration of a Cy hexane extract (especially 180 mg/Kg) reduced the numbers of leukocytes/eosinophils in BAL; the eosinophil peroxidase activity in BAL; the infiltration of leukocytes in lung tissue; the production of mucus in the respiratory tract; the level of IL-4 in BAL and the nuclear expression of NF-κB. CONCLUSIONS: The results presented demonstrate the potential of the Cy hexane extract to modulate allergic asthma; this extract may be an alternative future approach to treat this patholog