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- ItemAcesso aberto (Open Access)Papel dos ácidos graxos de cadeia curta na ativação do inflamassoma NLRP3 em modelo de asma grave(Universidade Federal de São Paulo (UNIFESP), 2019-12-18) Souza, Barbara Silva Tage De [UNIFESP]; Carvalho, Flavio Aimbire Soares De [UNIFESP]; http://lattes.cnpq.br/8216583445045638; http://lattes.cnpq.br/3315501610415715; Universidade Federal de São Paulo (UNIFESP)Introduction: Severe asthma is currently characterized by the presence of neutrophils, Th1 and Th17 cytokines, and resistance to corticosteroid therapy even at high doses. In this context, alternative therapies such as short chain fatty acids (SCFAs) are intended to be associated with corticotherapy to reduce their use due to their side effects. SCFAs appear to influence mechanisms of innate immunity. SCFAs influence immune system cells such as macrophages and neutrophils and appear to be involved with the receptor of innate immunity, NLRP3. In this context, this sensor has been linked to the developmente of severe asthma in humans. However, its role in severe asthma is not known. Objectives: Our objective was to evaluate the performance of SCFAs in the murine model of severe asthma and its influence on NLRP3. Methods: 6-10 mice/group were sensitized and challenged with 10 ug HDM in 80 uL PBS via i.t. on days 0 and 6-10. In the control group, animals were treated with PBS via i.t. during the same period. In SCFA-groups, the dose was 200mM in 100 ul PBS via gavage at the challenge period 1x/ day. Control group received 100 ul PBS via gavage during the same period. Animals were euthanized on the 15th day and the lungs and bronchoalveolar lavage was collected. Results: Our severe asthma model was characterized by cellularity, cytokine secretion, mucus and collagen deposition in the airways. SCFAs reduced the parameters associated with airway inflammation. Butyrate reduced the percentage of positive cells for NLRP3 expression in the peribronchial region. The absence of NLRP3 affected tissue remodeling and macrophage polarization. Conclusion: Butyrate influenced NLRP3 expression, which seems to be involved with tissue remodeling and pulmonary macrophages.