Class-Specific Histone Deacetylase Inhibitors Promote 11-Beta Hydroxysteroid Dehydrogenase Type 2 Expression in JEG-3 Cells.
Exposure to maternal cortisol plays a crucial role in fetal organogenesis. However, fetal overexposure to cortisol has been linked to a range of short- and long-term adverse outcomes. Normally, this is prevented by the expression of an enzyme in the placenta called 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2) which converts active cortisol to its inactive metabolite cortisone. Placental 11β-HSD2 is known to be reduced in a number of adverse pregnancy complications, possibly through an epigenetic mechanism. As a result, a number of pan-HDAC inhibitors have been examined for their ability to promote 11β-HSD2 expression. However, it is not known if the effects of pan-HDAC inhibition are a general phenomenon or if the effects are dependent upon a specific class of HDACs. Here, we examined the ability of pan- and class-specific HDAC inhibitors to regulate 11β-HSD2 expression in JEG3 cells. We find that pan-, class I, or class IIa HDAC inhibition promoted 11β-HSD2 expression and prevented cortisol or interleukin-1β-induced decrease in its expression. These results demonstrate that targeting a specific class of HDACs can promote 11β-HSD2 expression in JEG3 cells. This adds to the growing body of evidence suggesting that HDACs may be crucial in maintaining normal fetal development.
Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, University College Cork, Cork, Ireland; APC Microbiome Institute, Biosciences Institute, University College Cork, Cork, Ireland; INFANT Centre, Cork University Maternity Hospital, University College Cork, Cork, Ireland.
Katie L
KL
Togher
Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, University College Cork, Cork, Ireland; INFANT Centre, Cork University Maternity Hospital, University College Cork, Cork, Ireland.
Louise C
LC
Kenny
APC Microbiome Institute, Biosciences Institute, University College Cork, Cork, Ireland; INFANT Centre, Cork University Maternity Hospital, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Gerard W
0000-0001-5149-0933
GW
O'Keeffe