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Mediators of Inflammation
Volume 2012, Article ID 159709, 5 pages
http://dx.doi.org/10.1155/2012/159709
Research Article

Epigenetic Regulation of Cytokine Production in Human Amnion and Villous Placenta

1The University of Queensland Centre for Clinical Research, Royal Brisbane Hospital, Building 71/918, Herston, QLD 4029, Australia
2The Liggins Institute, University of Auckland, 2-6 Park Avenue, Private Bag 92019, Auckland 1023, New Zealand

Received 13 January 2012; Accepted 11 March 2012

Academic Editor: Felipe Vadillo-Ortega

Copyright © 2012 Murray D. Mitchell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The mechanisms of human preterm labour appear inextricably linked to cytokine biosynthesis by gestational tissues. In turn, cytokine production by gestational tissues has been shown to be regulated by epigenetic mechanisms. In this paper, we demonstrate that cytokine production in gestational tissues is regulated epigenetically in a tissue-specific manner. Furthermore, we show that treatment with a histone deacetylation inhibitor can partially abrogate LPS-stimulated TNFα production in villous placenta but not amnion. LPS treatment significantly ( 𝑃 < 0 . 0 5 ) increased the production of IL-1β (~10–34-fold), TNFα (~23–>100-fold) and IL10 (~6–10-fold) after 24 h of treatment in villous explants, as expected. There were no significant LPS effects on IL1Ra production. AZA treatment did not have any significant effect on any cytokines' production tested either alone or in combination with LPS. Interestingly, however, the stimulatory effects of LPS on TNFα production were partially mitigated ( 𝑃 < 0 . 0 5 ) by TSA treatment in villous explants. We suggest caution in the consideration of histone deacetylation inhibitors in pregnancy due to the different responses in gestational tissues.