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Título: Epigenetic profile in lipopolysaccharide-stimulate macrophages
Parte de: IMMUNOLOGY, v.137, suppl.1, Special Issue, p.591-591, 2012
Resumo: Purpose/Objective: Sepsis remains a clinical challenge for the intensive care units. However, it is known that the tolerance mechanism using low doses of lipopolysaccharide (LPS) reduces the expression of proinflammatory genes and involves epigenetic regulation. The chromatin openness is regulated by Histone Acetyltransferases (HATs) and these enzymes could be modulated by Nitric Oxide (NO) interaction. In the present work, we demonstrate the pathway of tolerance to LPS from HAT activity and level of histone openness to production of cytokines as well as the influence of NO inhibition. Materials and methods: THP1 differentiated into macrophages (with 2.5 nM PMA treatment) were cultivated in RPMI medium (Control group), submitted to tolerance (500 ng/ml of LPS 24 h before challenge with 1000 ng/ml of LPS * Tolerant group) and challenge (1000 ng/ml of LPS * D group) during 24 h. NO production was inhibited by addition of 100 l M of LNAME. The HAT activity and cytokine production (IL-6) were measured with biochemistry kits. Histone acetylated H3 and H4 were analyzed by western blotting. Results: Tolerance reduced HAT activity compared with group directly challenged (P< 0.05). The H4 acetylated was maintained at basal levels in the tolerant group and increased in the D group (P< 0.05). However, the tolerance increases the acetylation of Histone H3 in a NO-dependent response. Similarly, the IL-6 release was reduced by induction of tolerance (P< 0.05 versus D). However, this effect was abolished by inhibition of NO production. Conclusions: The induction of tolerance reduces HAT activity and cytokine production. The tolerance triggers a complex epigenetic modulation dependent of Nitric Oxide.
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Comunicações em Eventos - FM/MCM
Departamento de Clínica Médica - FM/MCM

Comunicações em Eventos - HC/ICHC
Instituto Central - HC/ICHC

Comunicações em Eventos - LIM/51
LIM/51 - Laboratório de Emergências Clínicas

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