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Effect of the tolerance to LPS in the cytokine production and activity of epigenetic enzymes in endotoxemic mice
Author(s) -
Rios Ester Correia Sarmento,
Lima Thais Martins,
Soriano Francisco Garcia
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb96
Subject(s) - acetylation , histone acetyltransferases , histone h4 , histone , epigenetics , cytokine , immunology , histone deacetylase , microbiology and biotechnology , endocrinology , medicine , chemistry , biology , biochemistry , gene
Epigenetic alteration could be associated to pre‐conditioning procedures. Chromatin remodeling in LPS tolerance is achieved by histone acetylation. LPS low doses induce a gene hypo‐transcription in acute immune response. We investigated how the tolerance to LPS could regulate the epigenetic response in the endotoxemia. Male “Balb C” mice were divided in: C group – control, not manipulated; TD group – induced tolerance and challenged ‐1mg/Kg LPS during 5 days before the challenge (5mg/Kg LPS); D group – challenged without tolerance ‐ 100μL of NaCl 0.9% during 5 days before the challenge (5mg/kg LPS). Spleens and plasma were collected 48 hours after the challenge. Activity of Histone Acetyltransferases (HAT) and Histone Deacetylases (HDAC) were assessed by colorimetric kits (abcam and biovision); Acetylation of histones H3 and H4 were analyzed by western blotting; cytokines production was measured by ELISA. Results represent the media of 5 animals. Statistical analysis was performed by ANOVA. Production of IL‐6, IL‐10 and TNF‐α was inhibited by the induction of the tolerance compared to D group. HAT and HDAC activities were increased in the TD group compared to C/D groups (p<0.05). H3 acetylated was reduced in TD compared to D. H4 acetylated was maintained at basal levels in TD and D groups. In conclusion, the reduction of cytokines during the tolerance to LPS is associated to H3 acetylation. Supported by FAPESP.