PT  - JOURNAL ARTICLE
AU  - Mohammed Alqinyah
AU  - Nagini Maganti
AU  - Mourad W Ali
AU  - Ruchi Yadav
AU  - Mei Gao
AU  - Han-Rong Weng
AU  - Susanna F Greer
AU  - Shelley B Hooks
TI  - Regulator of G-protein Signaling 10 (RGS10) expression is transcriptionally silenced in activated microglia by histone deacetylase activity
AID  - 10.1124/mol.116.106963
DP  - 2016 Jan 01
TA  - Molecular Pharmacology
PG  - mol.116.106963
4099  - http://molpharm.aspetjournals.org/content/early/2016/12/28/mol.116.106963.short
4100  - http://molpharm.aspetjournals.org/content/early/2016/12/28/mol.116.106963.full
AB  - RGS10 has emerged as a key regulator of pro-inflammatory cytokine production in microglia, functioning as an important neuroprotective factor. While RGS10 is normally expressed in microglia at high levels, expression is silenced in vitro following activation of TLR4 receptor. Given the ability of RGS10 to regulate inflammatory signaling, dynamic regulation of RGS10 levels in microglia may be an important mechanism to tune inflammatory responses. The goals of the current study were to confirm that RGS10 is suppressed in an in vivo inflammatory model of microglial activation and to determine the mechanism for activation-dependent silencing of Rgs10 expression in microglia. We demonstrate that endogenous RGS10 is present in spinal cord microglia, and RGS10 protein levels are suppressed in the spinal cord in a nerve injury induced neuropathic pain mouse model. We show that the HDAC enzyme inhibitor Trichostatin A blocks the ability of LPS to suppress Rgs10 transcription in BV-2 and primary microglia, demonstrating that HDAC enzymes are required for LPS silencing of Rgs10. Further, we used chromatin immunoprecipitation to demonstrate that H3 histones at the Rgs10 proximal promoter are deacetylated in BV-2 microglia following LPS activation, and HDAC1 association at the Rgs10 promoter is enhanced following LPS stimulation. Finally, we have shown that sphingosine 1-phosphate, an endogenous microglial signaling mediator which inhibits HDAC activity, enhances basal Rgs10 expression in BV-2 microglia, suggesting that Rgs10 expression is dynamically regulated in microglia in response to multiple signals.