title: Class I to III histone deacetylases differentially regulate inflammation-induced matrix metalloproteinase 9 expression in primary amnion cells.
abstract: Matrix metalloproteinase (MMP) 9 plays an important role in the degradation of the extracellular matrix in fetal membranes, and pathological activation of MMP-9 can lead to preterm birth. In nongestational tissues, modulation of histone deacetylases (HDACs) regulates MMP-9 expression. The aim of this study was to determine whether class I to III HDACs regulate MMP-9 expression and activity in primary amnion cells. Class I and II HDAC regulation of MMP-9 was assessed using the general class I and II HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), the class I HDACi MS-275, and the class II HDACi MC1568. Class III HDAC regulation of MMP-9 was assessed using the SIRT1 activators resveratrol and SRT1720 as well as SIRT1 small interfering RNA (siRNA). Primary amnion epithelial cells were incubated with 1 ng/mL interleukin (IL) 1β in the absence or presence of 0.3 μmol/L TSA, 5 μmol/L SAHA, 2.5 μmol/L MS-275, 2.5 μmol/L MC1568, 50 μmol/L resveratrol, or 10 μmol/L SRT1720 for 20 hours. We found that the class I and II HDACi TSA and SAHA and the class II HDACi MC1568 significantly decreased IL-β-induced MMP-9 gene and pro-MMP-9 expression in primary amnion cells. There was, however, no effect of the class I HDACi MS-275 on IL-β-induced MMP-9 expression. On the other hand, inhibition of class III HDAC SIRT1 using siRNA significantly augmented IL-1β-induced MMP-9, and SIRT1 activation using resveratrol and SRT1720 inhibited IL-1β-induced MMP-9 expression. In summary, class I to III HDACs differentially regulate inflammation-induced MMP-9 expression in primary amnion cells.
authors.affiliation: 1Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
authors.forename: Marin
authors.initials: M
authors.lastname: Poljak
authors.forename: Ratana
authors.initials: R
authors.lastname: Lim
authors.forename: Gillian
authors.initials: G
authors.lastname: Barker
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D000650:Amnion / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D056545:Group III Histone Deacetylases / Q000037:antagonists & inhibitors / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D056572:Histone Deacetylase Inhibitors; D034741:RNA, Small Interfering; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D056545:Group III Histone Deacetylases; D006655:Histone Deacetylases
keywords: MMP-9; SIRT1; fetal membranes; histone deacetylation