التفاصيل البيبلوغرافية
| العنوان: |
Histone deacetylase (HDAC) inhibitors reduce the glial inflammatory response in vitro and in vivo |
| المؤلفون: |
Giuseppe Faraco, Maria Pittelli, Leonardo Cavone, Silvia Fossati, Marco Porcu, Paolo Mascagni, Gianluca Fossati, Flavio Moroni, Alberto Chiarugi |
| المصدر: |
Neurobiology of Disease, Vol 36, Iss 2, Pp 269-279 (2009) |
| بيانات النشر: |
Elsevier, 2009. |
| سنة النشر: |
2009 |
| المجموعة: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| مصطلحات موضوعية: |
Transcription, NFκB, c-FOS, Microglia, SOCS, microRNA-146, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: |
Histone deacetylase inhibitors (HDACi) are emerging tools for epigenetic modulation of gene expression and suppress the inflammatory response in models of systemic immune activation. Yet, their effects within the brain are still controversial. Also, whether HDACs are expressed in astrocytes or microglia is unclear. Here, we report the identification of transcripts for HDAC 1–11 in cultured mouse glial cells. Two HDACi such as SAHA and ITF2357 induce dramatic increase of histone acetylation without causing cytotoxicity of cultured cells. Of note, the two compounds inhibit expression of pro-inflammatory mediators by LPS-challenged glial cultures, and potentiate immunosuppression triggered by dexamethasone in vitro. The anti-inflammatory effect is not due to HDACi-induced transcription of immunosuppressant proteins, (including SOCS-1/3) or microRNA-146. Rather, it is accompanied by direct alteration of transcription factor DNA binding and ensuing transcriptional activation. Indeed, both HDACi impair NFκB-dependent IκBα resynthesis in glial cells exposed to LPS, and, among various AP1 subunits and NFκB p65, affect the DNA binding activity of c-FOS, c-JUN and FRA2. Importantly, ITF2357 reduces the expression of pro-inflammatory mediators in the striatum of mice iontophoretically injected with LPS. Data demonstrate that mouse glial cells have ongoing HDAC activity, and its inhibition suppresses the neuroinflammatory response because of a direct impairment of the transcriptional machinery. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1095-953X |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S0969996109001880; https://doaj.org/toc/1095-953X |
| DOI: |
10.1016/j.nbd.2009.07.019 |
| URL الوصول: |
https://doaj.org/article/5f65e428ed664f81bcd672e70498f06b |
| رقم الانضمام: |
edsdoj.5f65e428ed664f81bcd672e70498f06b |
| قاعدة البيانات: |
Directory of Open Access Journals |