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GuaLou GuiZhi decoction represses LPS-induced BV2 activation via miR-155 induced inflammatory signals
Haixia Hu1, Xiaoqin Zhu2, Xinjun Lin3
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, China/Fujian Key Laboratory of Rehabilitation Technology, 13 Hudong branch Road, Fuzhou, Fujian, China/Fujian Key Laboratoty of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian, China.
Abstract:
Inflammatory response that occur post-ischemia is a serious problem in the treatment of ischemic brain disease. MicroRNA-155 is a brain-specific or brain-enriched miRNA, which mediates inflammatory reactions in cerebral ischemic tissue by regulating inflammatory signal and the expression level of SOCS1. The present study was aimed to assess the effect of GuaLou GuiZhi Decoction (GLGZD) on miR-155 expression in activated microglia following inflammation and further explore the role of GLGZD on expression of the inflammation-related gene. BV2 cells were used to simulated by LPS to make the inflammatory model. Expression level of miR-155 was detected by Real-Time PCR. BV2 cells after simulated by LPS were then transfected with miR-155 mimic and its negative controls. Cytokines release were measured by corresponding purchased ELISA kits, respectively. Then target protein expression of miR-155 were detected by western blotting assay. After miRNA over expression transfections, expressions of inflammation-related factors, SOCS-1 and SAMD in BV2 cells after activation were measured by Western blot assay. Results showed that in BV2 cells after simulated by LPS, miR-155 was upregulated. The elevated miR-155 expression enhanced the inflammatory cytokine release. miR-155 directly target and negatively regulated SOCS-1 and SMAD-1 expression. Over expression of SOCS-1 and SMAD reduced inflammatory action that was enhanced by miR-155 mimic transfection. miR-155 was positively related with activation of NF-ϰB signal pathways via SOCS-1 and SMAD. In conclusion, GuaLou GuiZhi Decoction (GLGZD) might exert its anti-inflammatory action by inhibiting the expression of miR-155, indicating that miR-155 may be used as a treatment target in clinical treatment with GuaLou GuiZhi Decoction (GLGZD) in ischemic brain.
Insights
GuaLou GuiZhi Decoction (GLGZD) may treat ischemic brain disease by reducing microRNA-155 (miR-155) expression. This inhibition lessens inflammation and cytokine release, offering a potential therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Post-ischemic inflammation poses a significant challenge in treating ischemic brain diseases.
- MicroRNA-155 (miR-155), a brain-enriched microRNA, plays a key role in mediating inflammatory responses within cerebral ischemic tissues by regulating inflammatory signaling pathways and SOCS1 expression.
Purpose of the Study:
- To investigate the effect of GuaLou GuiZhi Decoction (GLGZD) on miR-155 expression in activated microglia.
- To explore GLGZD's role in modulating inflammation-related gene expression.
Main Methods:
- An in vitro inflammatory model was established using BV2 cells stimulated with lipopolysaccharide (LPS).
- miR-155 expression levels were quantified using Real-Time PCR.
- BV2 cells were transfected with miR-155 mimics to assess its functional impact.
- Cytokine release was measured via ELISA, and target protein expression (SOCS-1, SMAD-1) was analyzed by Western blotting.
Main Results:
- LPS stimulation led to the upregulation of miR-155 in BV2 cells, correlating with increased inflammatory cytokine release.
- miR-155 was found to directly target and negatively regulate SOCS-1 and SMAD-1 expression.
- Overexpression of SOCS-1 and SMAD-1 attenuated the miR-155 mimic-induced inflammatory response.
- miR-155 positively correlated with the activation of NF-κB signaling pathways through SOCS-1 and SMAD-1.
Conclusions:
- GuaLou GuiZhi Decoction (GLGZD) demonstrates potential anti-inflammatory effects in ischemic brain conditions by inhibiting miR-155 expression.
- miR-155 emerges as a potential therapeutic target for clinical interventions involving GLGZD in ischemic brain disease treatment.
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