Gα13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia

Bettegazzi, Barbara; Bellani, Serena; Cattaneo, Stefano; Codazzi, Franca; Grohovaz, Fabio; Zacchetti, Daniele

doi:10.1007/s12035-021-02553-0

Cited by 7 publications

(6 citation statements)

References 98 publications

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“…In our hands, however, the cellular composition was constant across different experiments. Primary mixed cell cultures have, indeed, the ability to reproduce various established physiological properties of microglia such as migration, the ingestion of debris, and the secretion of pro-inflammatory cytokines and chemokines upon activation [22,23]; microglial cells closely cooperate with astrocytes, which play an essential role in maintaining the local physiological microenvironment by controlling potassium and neurotransmitter levels, thereby exerting a profound influence on neuronal excitability [24]. were treated with LPS (100 ng/mL) for 24 h and then with FGF-2/BDNF for 48 h. Releases of cytokines and NO were evaluated as described in Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation

Aziz,

Ruzza,

Falcicchia

et al. 2024

IJMS

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Neuroinflammation is associated with several neurological disorders including temporal lobe epilepsy. Seizures themselves can induce neuroinflammation. In an in vivo model of epilepsy, the supplementation of brain-derived neurotropic factor (BDNF) and fibroblast growth factor-2 (FGF-2) using a Herpes-based vector reduced epileptogenesis-associated neuroinflammation. The aim of this study was to test whether the attenuation of the neuroinflammation obtained in vivo with BDNF and FGF-2 was direct or secondary to other effects, for example, the reduction in the severity and frequency of spontaneous recurrent seizures. An in vitro model of neuroinflammation induced by lipopolysaccharide (LPS, 100 ng/mL) in a mouse primary mixed glial culture was used. The releases of cytokines and NO were analyzed via ELISA and Griess assay, respectively. The effects of LPS and neurotrophic factors on cell viability were determined by performing an MTT assay. BDNF and FGF-2 were tested alone and co-administered. LPS induced a significant increase in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NO. BDNF, FGF-2, and their co-administration did not counteract these LPS effects. Our study suggests that the anti-inflammatory effect of BDNF and FGF-2 in vivo in the epilepsy model was indirect and likely due to a reduction in seizure frequency and severity.

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Section: Discussionmentioning

confidence: 99%

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation

Aziz,

Ruzza,

Falcicchia

et al. 2024

IJMS

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“…The normal function of microglia is to migrate precisely to sites of neural injury. The role of overactivation of microglia induced by lipopolysaccharide, a prominent cell wall component of gram‐negative bacteria, in promoting migration has been extensively studied 19,20 . Interestingly, transwell migration assay results showed that the Treponema pallidum membrane protein Tp47 inhibited microglial migration, showing an effect opposite that of bacterial lipopolysaccharide.…”

Section: Discussionmentioning

confidence: 99%

“…The role of overactivation of microglia induced by lipopolysaccharide, a prominent cell wall component of gram-negative bacteria, in promoting migration has been extensively studied. 19,20 Interestingly, transwell migration assay results showed that the F I G U R E 5 PI3K/AKT promoted Tp47induced autophagy through FOXO1. (A) The effect of the PI3K/AKT agonist 740 Y-P and inhibitor LY294002 on the protein levels of p-FOXO1.…”

Section: Discussionmentioning

confidence: 99%

Treponema pallidum membrane protein Tp47 induced autophagy and inhibited cell migration in HMC3 cells via the PI3K/AKT/FOXO1 pathway

Xie

Zheng

et al. 2023

J Cellular Molecular Medi

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The migratory ability of microglia facilitates their rapid transport to a site of injury to kill and remove pathogens. However, the effect of Treponema pallidum membrane proteins on microglia migration remains unclear. The effect of Tp47 on the migration ability and autophagy and related mechanisms were investigated using the human microglial clone 3 cell line. Tp47 inhibited microglia migration, the expression of autophagy‐associated protein P62 decreased, the expression of Beclin‐1 and LC3‐II/LC3‐I increased, and the autophagic flux increased in this process. Furthermore, autophagy was significantly inhibited, and microglial cell migration was significantly increased after neutralisation with an anti‐Tp47 antibody. In addition, Tp47 significantly inhibited the expression of p‐PI3K, p‐AKT, and p‐mTOR proteins, and the sequential activation of steps in the PI3K/AKT/mTOR pathways effectively prevented Tp47‐induced autophagy. Moreover, Tp47 significantly inhibited the expression of p‐FOXO1 protein and promoted FOXO1 nuclear translocation. Inhibition of FOXO1 effectively suppressed Tp47‐induced activation of autophagy and inhibition of migration. Treponema pallidum membrane protein Tp47‐induced autophagy and inhibited cell migration in HMC3 Cells via the PI3K/AKT/FOXO1 pathway. These data will contribute to understanding the mechanism by which T. pallidum escapes immune killing and clearance after invasion into the central nervous system.

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“…We also found that LPS transformed microglial morphology from a polarized baseline state to an ameboid-like state, and NaE pre-treatment prevented these changes. It is well accepted that LPS-induced morphological and functional changes are related to cytoskeletal rearrangement, F-actin being the major contributor, and research on natural products has documented their efficacy in ameliorating these cytoskeletal organization variations [59][60][61]. Since NaE affected the migration capacity of BV2 cells, to investigate NaE actions regarding actin cytoskeletal morphology represents a forthcoming challenge.…”

Section: Discussionmentioning

confidence: 99%

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

et al. 2023

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Microglia, the resident macrophage-like population in the CNS, plays an important role in the pathogenesis of many neurodegenerative disorders. Nectandra genus is known to produce different metabolites with anti-inflammatory, anti-oxidant and analgesic properties. Although the species Nectandra angustifolia is popularly used for the treatment of different types of inflammatory processes, its biological effects on neuroinflammation have not yet been addressed. In this study, we have investigated the role of a Nectandra angustifolia ethanolic extract (NaE) in lipopolysaccharide (LPS)-induced neuroinflammation in vitro and in vivo. In LPS-activated BV2 microglial cells, NaE significantly reduced the induced proinflammatory mediators TNF-α, IL-1β, IL-6, COX-2 and iNOS, as well as NO accumulation, while it promoted IL-10 secretion and YM-1 expression. Likewise, reduced CD14 expression levels were detected in microglial cells in the NaE+LPS group. NaE also attenuated LPS-induced ROS and lipid peroxidation build-up in BV2 cells. Mechanistically, NaE prevented NF-κB and MAPKs phosphorylation, as well as NLRP3 upregulation when added before LPS stimulation, although it did not affect the level of some proteins related to antioxidant defense such as Keap-1 and HO-1. Additionally, we observed that NaE modulated some activated microglia functions, decreasing cell migration, without affecting their phagocytic capabilities. In LPS-injected mice, NaE pre-treatment markedly suppressed the up-regulated TNF-α, IL-6 and IL-1β mRNA expression induced by LPS in brain. Our findings indicate that NaE is beneficial in preventing the neuroinflammatory response both in vivo and in vitro. NaE may regulate microglia homeostasis, not only restraining activation of LPS towards the M1 phenotype but promoting an M2 phenotype.

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Gα13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia

Cited by 7 publications

References 98 publications

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation

Treponema pallidum membrane protein Tp47 induced autophagy and inhibited cell migration in HMC3 cells via the PI3K/AKT/FOXO1 pathway

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

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