Triggering Receptor Expressed on Myeloid Cell-2 Protects PC12 Cells Injury by Inhibiting BV2 Microglial Activation

Ni, Jian-Wu; Li, Caixia; Chen, Xiongwei; Cai, Wenpin

doi:10.4103/0028-3886.364080

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…Studies have suggested that trem2-negative microglia are more activated than trem2-expressing microglia; in vitro, exposure to LPS/IFNγ dramatically reduced microglial expression of trem2 [ 39 ]. Knockdown of trem2 in BV2 cells increased LPS-stimulated NO production [ 20 , 40 ]. These results enhanced the relationship between trem2 and glioma cytotoxic NO.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways

Yan,

Bai,

Han

et al. 2024

Cell Commun Signal

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Background In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. Methods Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2’-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. Results Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β, and caused further DNA damage and promoted the apoptosis rate of tumor cells. Conclusions Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

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Section: Discussionmentioning

confidence: 99%

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways

Yan,

Bai,

Han

et al. 2024

Cell Commun Signal

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“…In APP/PS1 mice, upregulation of TREM2 can inhibit GSK-3β, the major kinase involved in Tau hyperphosphorylation in AD, by activating the PI3K/Akt signaling pathway, thereby inhibiting the phosphorylation of Tau protein, and has similar effects in SH-SY5Y cells (Peng et al, 2023). In BV2 cells, TREM2 can inhibit LPS-mediated neuronal apoptosis by downregulating inducible iNOS (M1) and upregulating Arg-1 expression in BV2 microglia (Ni et al, 2022). Another study found that LP17, the synthetic peptide blocker of TREM1, inhibited 6hydroxydopamine-induced locomotor defects and iNOS messenger RNA expression in rat and zebrafish PD models (Feng et al, 2019).…”

Section: Expression Of Trem2 and Dual Roles Of Trem2 In Admentioning

confidence: 99%

The role of TREM2 in Alzheimer’s disease: from the perspective of Tau

Huang,

Huang

et al. 2023

Front. Cell Dev. Biol.

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Triggering receptor expressed on myeloid cells 2 (TREM2), a pattern recognition receptor abundantly expressed on microglia, has been identified as one of the risk factors for Alzheimer’s disease (AD). Several studies have already demonstrated the relationship between TREM2 and Tau. TREM2 mutations and altered expression play an important role in Tau phosphorylation. Furthermore, the level of Tau phosphorylation is correlated with soluble TREM2 (sTREM2). However, in different stages of AD, TREM2 seems to have varying effects on Tau pathology. The explicit interaction between TREM2 and Tau, as well as how they affect AD pathology, remains unclear, and there is much evidence to the contrary that requires rational interpretation. Reviewing the dual roles of TREM2 in AD will help identify a more appropriate development strategy for targeting TREM2 to treat AD. Therefore, this review focuses on the interplay between Tau and TREM2 in relation to AD.

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Nicotinic acid modulates microglial TREM-2 gene in Phytohaemagglutinin-Induced in vitro model of Alzheimer’s disease like pathology

Amir,

Shahid,

Farooq Khan

et al. 2024

Brain Research

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Triggering Receptor Expressed on Myeloid Cell-2 Protects PC12 Cells Injury by Inhibiting BV2 Microglial Activation

Cited by 3 publications

References 18 publications

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways

The role of TREM2 in Alzheimer’s disease: from the perspective of Tau

Nicotinic acid modulates microglial TREM-2 gene in Phytohaemagglutinin-Induced in vitro model of Alzheimer’s disease like pathology

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