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Am J Physiol Endocrinol Metab 290: E490-E493, 2006. First published October 18, 2005; doi:10.1152/ajpendo.00406.2005
0193-1849/06 $8.00
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Molecular inhibition of histone deacetylation results in major enhancement of the production of IL-1beta in response to LPS

Timothy A. Sato1 and Murray D. Mitchell1,2

1Liggins Institute, University of Auckland; and 2National Research Centre for Growth and Development, Auckland, New Zealand

Submitted 26 August 2005 ; accepted in final form 12 October 2005

It has been postulated that the progression of human pregnancy to term is, in part, the result of a relative maternal Th2 immunological state. This can be activated in some cell types by modifying DNA methylation and histone acetylation status. We demonstrate that the molecular inhibition of histone deacetylation, using trichostatin A (TSA), in human choriodecidual explants leads to a massive increase in lipopolysaccharide (LPS)-stimulated IL-1beta. The inhibition of histone deacetylation had no effect on LPS-stimulated TNF-{alpha} production or production of the other cytokines studied (IL-10, IL-1 receptor antagonist). The molecular inhibition of DNA methylation and histone deacetylation, using 5-aza-2'-deoxycytidine and TSA, respectively, in human choriodecidual explants also results in an increase in the basal production of TNF-{alpha} but not that of IL-1beta. The differential response is unique, and the relative uncoupling of IL-1beta and TNF-{alpha} responsiveness may have importance in other biological systems and provide new therapeutic targets for pathologies where upregulation of IL-1beta is known to be a causative factor.

interleukin-1beta; lipopolysaccharide; histane deacetylation; human pregnancy


Address for reprint requests and other correspondence: M. D. Mitchell, Liggins Institute, Faculty of Medical and Health Sciences, Univ. of Auckland, Private Bag 92019, Auckland, New Zealand (e-mail: m.mitchell{at}auckland.ac.nz)






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