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Published on: January 30, 2014
Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis
Xi Xiao1,2, Yuanyuan Hou1,2, Wei Yu1
1Department of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, Harbin, 150001 Heilongjiang Province, China.
Background:
Propofol is a widely used intravenous anesthetic drug with potential neuroprotective effect in diverse diseases of neuronal injuries such as traumatic brain injury and ischemic stroke. However, the underlying molecular mechanism remains largely unknown.
Methods:
Real-time qPCR, enzyme-linked immunosorbent assay, and Western blotting were used to identify the expression pattern of miR-221/222, inflammatory genes, cytokines, and IRF2. The biological roles and mechanisms of propofol in microglia activation were determined in BV2 cells and primary microglia. Bioinformatic analysis and luciferase reporter assay were used to confirm the regulatory role of miR-221/222 in Irf2 expression.
Results:
We found that miR-221 and miR-222 were downstream targets of propofol and were consistently upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Gain- and loss-of-function studies revealed that miR-221 and miR-222 were profoundly implicated in microglia activation. Then, interferon regulatory factor 2 (Irf2) was identified as a direct target gene of miR-221/222. IRF2 protein levels were reduced by miR-221/222 and increased by propofol treatment. Ectopic expression of IRF2 attenuated the proinflammatory roles induced by LPS in BV2 cells. More importantly, the suppressive effects of propofol on LPS-primed activation of BV2 cells or primary mouse microglia involved the inhibition of miR-221/222-IRF2 axis.
Conclusions:
Our study highlights the critical function of miR-221/222, which inhibited Irf2 translation, in the anti-inflammatory effects of propofol, and provides a new perspective for the molecular mechanism of propofol-mediated neuroprotective effect.
Insights
Propofol’s neuroprotective effects involve inhibiting miR-221/222, which suppresses inflammatory factor IRF2. This reveals a key molecular mechanism for propofol’s anti-inflammatory action in brain injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Propofol, an anesthetic, shows potential neuroprotection in brain injuries like TBI and stroke.
- The precise molecular mechanisms underlying propofol's neuroprotective effects are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of propofol's anti-inflammatory and neuroprotective effects.
- To investigate the role of microRNAs (miRNAs) and their targets in propofol's action on microglia.
Main Methods:
- Real-time qPCR, ELISA, and Western blotting to analyze gene and protein expression.
- Cellular studies using BV2 cells and primary microglia to assess microglia activation.
- Bioinformatic analysis and luciferase reporter assays to confirm miRNA-target interactions.
Main Results:
- Propofol treatment modulated the expression of miR-221/222 and IRF2 in microglia.
- miR-221 and miR-222 were identified as direct targets of propofol and negatively regulated IRF2.
- Inhibition of the miR-221/222-IRF2 axis by propofol suppressed LPS-induced microglia activation.
Conclusions:
- miR-221/222 play a crucial role in the anti-inflammatory effects of propofol by inhibiting IRF2 translation.
- This study provides novel insights into the molecular basis of propofol's neuroprotective properties.
