Effect of DNA methylation and histone deacetylase inhibitors on cytokine production in the human placenta

Mitchell, Murray D., Ponnampalam, Anna P., Peiris, Hassebdrini and Rice, Gregory E. (2011). Effect of DNA methylation and histone deacetylase inhibitors on cytokine production in the human placenta. In: Abstracts of the 58th Annual Scientific Meeting of the Society for Gynecologic Investigation. 58th Annual Scientific Meeting of the Society for Gynecologic Investigation, Miami Beach FL, United States, (297A-297A). 16-19 March 2011. doi:10.1177/193371912011183s067


Author Mitchell, Murray D.
Ponnampalam, Anna P.
Peiris, Hassebdrini
Rice, Gregory E.
Title of paper Effect of DNA methylation and histone deacetylase inhibitors on cytokine production in the human placenta
Conference name 58th Annual Scientific Meeting of the Society for Gynecologic Investigation
Conference location Miami Beach FL, United States
Conference dates 16-19 March 2011
Proceedings title Abstracts of the 58th Annual Scientific Meeting of the Society for Gynecologic Investigation   Check publisher's open access policy
Journal name Reproductive Sciences   Check publisher's open access policy
Place of Publication Thousand Oaks, CA, United States
Publisher Sage Publications
Publication Year 2011
Sub-type Published abstract
DOI 10.1177/193371912011183s067
Open Access Status
ISSN 1933-7191
1933-7205
Volume 18
Issue 3, Supp.
Start page 297A
End page 297A
Total pages 1
Collection year 2012
Language eng
Formatted Abstract/Summary
Background: Parturition is characterized by increased production of inflammatory cytokines with subsequent increased intrauterine PG production which promotes contraction of the uterus. This mechanism is also recognised to be a major causative factor in the preterm initiation of labor leading to premature birth. However, the precise mechanism of this cytokine regulation is not well understood.

Objective:
To determine the effects of treatment with inhibitors of DNA methylation and histone deacetylation on LPS-stimulated prostaglandin and infl ammatory cytokine production in placental villous, amnion and choriodecidual explants.

Methods: Explants were isolated from term placental villous, amnion and choriodecidua and treated with 5-aza-2-deoxycytidine AZA (5mM or 200nM) for 2 days. After day 2, the explants were treated with the bacterial endotoxin lipopolysaccharide (LPS) at 5mg/ml and co-treated with or without 300nM trichostatin A (TSA, an inhibitor of histone deacetylation) Media were collected after 24 hours and analysed for IL-1β, TNFα, IL-10 and IL1ra content by ELISA.

Results:
LPS treatment significantly increased the production of proinflammatory cytokines IL-1β and TNFα in villous and chorio decidual explants. A dramatic increase in production of IL-1β was observed following treatment with TSA and AZA/TSA in LPS stimulated villous explants which were additional to the effects of stimulation, while AZA treatment did not have a significant effect. However, the effects of LPS on TNFα production were mitigated by TSA in villous explants. In contrast, the anti-inflammatory
cytokines IL-10 and IL1ra, while showing stimulation by LPS exhibited no other changes in response to treatment with AZA, TSA or AZA/TSA in all explants. The effects of TSA were not prominent in amnion and choriodecidual explants. Experiments to determine the effects of AZA and TSA on PGE2 production is in progress.

Conclusions:
Our preliminary data show that the production of proinflammatory cytokines in human placenta is altered by TSA treatment but not AZA treatment following LPS stimulation especially in villous explants. This suggests a role for epigenetic regulation of the pro-inflammatory cytokines, specifically through histone modifications.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published under Poster Session: Basic Parturition/Prematurity : Scientific Abstracts of the SGI 58th Annual Scientific Meeting: Reproduction and Regenerative Medicine.

Document type: Conference Paper
Collections: UQ Centre for Clinical Research Publications
Temporary Review
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Google Scholar Search Google Scholar
Created: Fri, 15 Jul 2011, 15:16:44 EST by System User on behalf of UQ Centre for Clinical Research