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Volume 17 Supplement 4

Sepsis 2013

  • Poster presentation
  • Open Access

Epigenetic profile in lipopolysaccharide-stimulated macrophages

  • 1,
  • 1 and
  • 1
Critical Care201317 (Suppl 4) :P88

  • Published:


  • Nitric Oxide
  • Western Blotting
  • Emergency Medicine
  • Cytokine Production
  • RPMI Medium


Sepsis remains a clinical challenge for the ICUs. 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 LPS 24 hours before challenge with 1,000 ng/ml LPS - Tolerant group) and challenge (1,000 ng/ml LPS - D group) during 24 hours. NO production was inhibited by addition of 100 μM LNAME. The HAT activity and cytokine production (IL-6) were measured with biochemistry kits. Histone acetylated H3 and H4 were analyzed by western blotting.


Tolerance reduced HAT activity compared with the group directly challenged (P < 0.05). Acetylated H4 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 vs. D group). However, this effect was abolished by inhibition of NO production.


The induction of tolerance diminishes HAT activity and cytokine production. The tolerance triggers a complex epigenetic modulation dependent of NO.



FAPESP 09/15530-0.

Authors’ Affiliations

Department of Emergency Medicine, University of São Paulo Medical School, Brazil


© Rios et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.