Histone deacetylase inhibitors valproic acid and sodium butyrate enhance prostaglandins release in lipopolysaccharide-activated primary microglia
Singh, V; Bhatia, HS; Kumar, A; de Oliveira, AC; Fiebich, BL
| HERO ID | 2284311 |
|---|---|
| In Press | No |
| Year | 2014 |
| Title | Histone deacetylase inhibitors valproic acid and sodium butyrate enhance prostaglandins release in lipopolysaccharide-activated primary microglia |
| Authors | Singh, V; Bhatia, HS; Kumar, A; de Oliveira, AC; Fiebich, BL |
| Journal | Neuroscience |
| Volume | 265 |
| Page Numbers | 147-157 |
| Abstract | Modifications of histone deacetylases (HDACs) may be involved in microglia-driven neuroinflammatory responses. Recent studies suggest that several inflammatory molecules can regulate the extent of neurodegeneration and regeneration in the central nervous system (CNS). In the present study, we investigated the effects of HDAC inhibitors (HDACi) valproic acid (VPA) and sodium butyrate (NaBut) on the release of prostaglandins (PGs) in lipopolysaccharide (LPS)-activated microglia. We found that VPA and NaBut significantly enhanced LPS-induced release of PGE2, PGD2 and 8-iso-PGF2α. In addition, both compounds increased cyclooxygenase-2 and microsomal prostaglandin E synthase immunoreactivity and gene expression in LPS-stimulated microglia. Interestingly, treatment of activated microglia with HDACi also enhanced the gene expression and the release of different pro-inflammatory cytokines. Microglia activation with LPS leads to IκB-α degradation, as well as p38, ERK1/2 and JNK MAPKs phosphorylation and thus activation, which is not affected by treatment with VPA and NaBut. Furthermore, VPA and NaBut treatment induced histone acetylation at H3-K18 in microglia. We suggest that VPA and NaBut-driven increase in PGs release in LPS-activated microglia might be regulated at the transcriptional level and involves histone hyperacetylation. Our data demonstrate that VPA and NaBut are able to modulate microglia responses to inflammatory insults and thus possibly can regulate the CNS degenerative and regenerative processes. |
| Doi | 10.1016/j.neuroscience.2014.01.037 |
| Pmid | 24480366 |
| Wosid | WOS:000334134400014 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | cyclooxygenase-2; microsomal prostaglandin E synthase-1; microglia; prostaglandin; histone deacetylase inhibitors |