JOURNAL OF CHEMICAL NEUROANATOMY
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2024
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IF 2.7
Lili Ma,Na Mi,Zhi Wang,Rui Bao,Jing Fang,Yajing Ren,Xiuzhi Xu,Hongjia Zhang,Ying Tang
Neuroinflammation associated with microglial activation plays a role in the development of Parkinson's disease (PD). The upregulation of interferon regulatory factor 8 (IRF8) in microglia following peripheral nerve injury has been observed to induce microglial activation. This suggests the potential therapeutic significance of IRF8 in PD. This research aims to explore the effects of IRF8 on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-induced neuroinflammation, along with its underlying mechanisms. The study examines the differential expression of IRF8 and its effects on neuropathological changes using a PD mouse model and a PD model established from BV2 cells in vitro . IRF8 was found to be prominently expressed in the substantia nigra pars compacta (SNpc) region of PD mice and LPS-stimulated BV2 cells, while the expression of tyrosine hydroxylase (TH) and dopamine (DA) content in the SNpc region of PD mice was notably reduced. MPTP treatment and LPS stimulation intensified microglial activation, inflammation, and activation of the AMPK/mTOR signaling pathway in vivo and in vitro , respectively. Upon IRF8 silencing in the PD mouse and cell models, the knockdown of IRF8 ameliorated MPTP-induced behavioral deficits, increased the counts of TH and Nissl-positive neurons and DA content, reduced the number of Iba-1-positive microglia, and reduced the content of inflammatory factors, possibly by inhibiting the AMPK/mTOR signaling pathway. Similar outcomes were observed in the PD cell model. In conclusion, the suppression of IRF8 alleviates neuroinflammation through regulating microglial activation in PD models in vivo and in vitro by the AMPK/mTOR signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF NEUROIMMUNOLOGY
·
2026
·
IF 3.1
Jingkun Wu,Liang Hou,Qinghua Zhu,Hongbin Wang,Naizhu Wang
Interferon regulatory factor 8 (Irf8) is a transcription factor expressed only in the microglia in the brain and directs the expression of many genes that serve microglial functions. This report investigates the role of Irf8 in microglia during the progression of hypertensive intracerebral hemorrhage (ICH). L-NAME and angiotensin II initiated the ICH mouse model after stereotactic injection of knockdown and overexpression vectors. Inflammatory responses were induced in the mouse microglia cell line BV-2 using lipopolysaccharide (LPS), and lentiviral infection was conducted to manipulate gene expression. Irf8 was significantly overexpressed in the brain tissues of ICH mice and LPS-induced BV-2 cells. Downregulation of Irf8 hampered microglial M1 polarization and the inflammatory response and partially alleviated limb dysfunction caused by neurological impairment resulting from ICH. Irf8 interacted with the signal transducer and activator of transcription 1 (Stat1), thus mediating the transcriptional activation of Stat1 on tripartite motif-containing protein 5 (Trim5) in microglia. Overexpression of Trim5 reversed the inhibitory effect of sh-Irf8 on the inflammatory response in microglia and exacerbated cerebral hemorrhage in ICH mice. Thus, it was suggested that Irf8 overexpression activated the Stat1/Trim5 axis and mediated a microglial proinflammatory phenotype, thereby exacerbating hypertensive ICH.
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PubMed
高影响因子
ACS Chemical Neuroscience
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2024
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IF 4.1
Wei Du,Xiaomin Zhang,Songze Li,Xin Xie
This study aims to investigate the role of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction in newborn mice. Newborn mice were exposed to sevoflurane, followed by behavioral assessments and single-cell transcriptome sequencing of cortical cells. Lentivirus-mediated overexpression of neuronal SIRPα and assessment of the microglial morphology and synaptic function were conducted. Sevoflurane exposure resulted in social cognitive impairments without affecting motor coordination. Transcriptomic analysis revealed no significant changes in cortical microglial cells or neurons. However, sevoflurane inhibited nonsynaptic synapse modification by microglia. Overexpression of neuronal SIRPα enhanced microglial function, promoted neuron development, and ameliorated cognitive impairments. SCENIC analysis identified a correlation between IRF8 and SIRPα expression. This study sheds light on the involvement of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction. Understanding these mechanisms offers new avenues for exploring cognitive impairment pathways and potential therapeutic targets.
研究领域:
神经科学
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分子生物学
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发育生物学
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PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2026
·Vol. 83
·期 1
·76
·
IF 6.2
Feiyu Lu,Shengnan Wang,Mengru Zhu,Kuo Qu,Tong Zhu,Hong Wang,Yongli Yu,Liying Wang
The imbalanced expression of interferon regulatory factor (IRF) 4 and IRF8 in activated B cells significantly influences their differentiation and promotes the development of immune-related diseases. Restoring abnormal B cells to appropriate responses may treat these diseases. In this study, an oligodeoxynucleotide (ODN) S2, designed according to the consensus sequence recognized by IRFs in interferon-stimulated response elements, was used as an immunomodulator to investigate its effects on mouse splenic B cells stimulated with the TLR9 agonist CpG ODN, either alone or in combination with antigen, and to explore its underlying mechanisms. The results showed that S2 had a significant negative regulatory effect on CpG ODN induced B cell activation. It also significantly downregulated the production of IL-6 and the percentage of IL-6 + B cells in splenocytes stimulated by CpG ODN, but significantly upregulated the percentage of IL-10 + B cells. Interestingly, S2 impaired antibody production both in vitro and in vivo, but rescued mice from lethal inflammatory responses. Further studies showed that S2 could bind IRF4 and IRF8 with high affinity, slightly upregulate phosphorylated IRF4, reduce the expression and nuclear translocation of IRF8, and alter the proportion of IRF4 + , IRF8 + or double-positive B cells in spleen cells induced by CpG ODN. These results suggest that S2 acts as a decoy directing some B cells to differentiate into IL-10-producing Breg-like cells rather than plasma cells by restoring the TLR9 signal-induced IRF4 and IRF8 ratio imbalance. This indicates its potential as an immunomodulator for the treatment of diseases associated with B-cell abnormalities.
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高影响因子
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