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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1
Huaitao Yang1, Zhifang Chen2, Wenhong Gao1
1Department of Neurosurgery, Jingzhou Hospital Affiliated to Yangtze University, No. 26, Chuyuan Ave, Jingzhou District, Jingzhou, Hubei 434020, P.R. China.
Objective:
This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism.
Methods:
Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1β, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified.
Results:
OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation.
Conclusion:
Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.
Insights
Euchromatic histone lysine methyltransferase 2 (EHMT2) exacerbates ischemic stroke damage by promoting heme oxygenase 1 (HMOX1) expression. Down-regulating EHMT2 alleviates neuronal injury and inflammation by inhibiting HMOX1.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Ischemic stroke causes significant neuronal damage and inflammation.
- The role of euchromatic histone lysine methyltransferase 2 (EHMT2) in this process requires further elucidation.
Purpose of the Study:
- To investigate the function of EHMT2 in ischemic stroke-induced neuronal damage and inflammation.
- To explore the regulatory mechanism of EHMT2 in this context.
Main Methods:
- Established a cellular model of ischemic stroke using oxygen-glucose deprivation/reoxygenation (OGD/R) in mouse microglia (BV-2 cells) co-cultured with HT22 neurons.
- Assessed neuronal viability, apoptosis, microglial polarization markers, inflammatory factors, and the expression and interaction of EHMT2 and heme oxygenase 1 (HMOX1).
Main Results:
- OGD/R induced neuronal damage and inflammatory response.
- EHMT2 and HMOX1 expression increased in OGD/R-treated microglia.
- Knockdown of EHMT2 or HMOX1 attenuated neuronal damage and inflammation.
- EHMT2 promotes HMOX1 transcription via histone methylation.
Conclusions:
- EHMT2 plays a detrimental role in ischemic stroke by upregulating HMOX1.
- Down-regulation of EHMT2 offers a potential therapeutic strategy by inhibiting HMOX1 and reducing neuronal damage and inflammation.
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