HIV-1 Tat drives the Fabp4/NF-κB feedback loop in microglia to mediate inflammatory response and neuronal apoptosis

Zhou, Xiaodan; Zhou, Shuhui; Ji, Tao; Gao, Yanan; Meng, Gaoqiang; Cao, Deliang; Lin, Guangyong

doi:10.1007/s13365-022-01094-z

Cited by 9 publications

(2 citation statements)

References 41 publications

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“…However, how FABP4 functions in microglia after ischemia remains unclear. Microglial FABP4 regulates neuroinflammation in obese mice [ 41 ] and in human immunodeficiency virus-1-associated neurocognitive disorder [ 42 ]. Further extensive studies are required to investigate the function of FABP4 in microglia after ischemia.…”

Section: Discussionmentioning

confidence: 99%

Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons

et al. 2023

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“…Neuroinflammation has also contributed to neurocognitive deficits of parasitic infections such as cerebral malaria [ 4 , 5 ]. The neuropathologies of viral infections such as HIV-associated neurocognitive disorder (HAND) and COVID-19 have been linked to brain inflammation [ 6 , 7 , 8 , 9 ]. Consequently, anti-inflammatory strategies are critical therapeutic modalities in these conditions.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

et al. 2023

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Skimmianine is a furoquinoline alkaloid which is found in the Zanthoxylum genus and also in other plants of the Rutaceae family. This study evaluated the effects of skimmianine on the production of pro-inflammatory mediators in LPS-activated BV-2 microglia. Cultured BV-2 cells were treated with skimmianine (10, 20 and 30 μM), followed by stimulation with LPS (100 ng/mL). Levels of TNFα and IL-6 in cell supernatants were measured using ELISA, while NO and PGE2 levels were evaluated with Griess assay and EIA, respectively. Western blotting was used to determine the protein expression of iNOS, COX-2, phospho-p65 and phospho-IκBα. Results showed that Skimmianine reduced LPS-induced elevated the secretion of TNFα, IL-6, NO, and PGE2, as well as the increased protein expression of iNOS and COX-2. Experiments to elucidate the mechanisms of the anti-neuroinflammatory activity of skimmianine revealed the significant inhibition of LPS-induced increased NF-κB-mediated luciferase activity. Pre-treatment with skimmianine also reduced LPS-induced the increased phosphorylation of NF-κB/p65 and IκBα proteins. Furthermore, skimmianine interfered with the binding capacity of NF-κB to consensus sites. Skimmianine pre-treatment protected HT-22 cells from toxicity induced by microglia-conditioned media, as well as increasing MAP-2 expression. The results of this study suggest that skimmianine inhibits neuroinflammation in LPS-activated microglia by targeting the NF-κB activation pathway. Skimmianine also produced neuroprotection against neurotoxicity induced by microglia-conditioned media.

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Fatty Acid-Binding Protein 4 is Essential for the Inflammatory and Metabolic Response of Microglia to Lipopolysaccharide

Kagawa,

Low,

Pyun

et al. 2023

J Neuroimmune Pharmacol

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Prolonged activation of microglia leads to excessive release of proinflammatory mediators, which are detrimental to brain health. Therefore, there are significant efforts to identify pathways mediating microglial activation. Recent studies have demonstrated that fatty acid-binding protein 4 (FABP4), a lipid binding protein, is a critical player in macrophage–mediated inflammation. Given that we have previously identified FABP4 in microglia, the aim of this study was to assess whether FABP4 activity contributed to inflammation, metabolism and immune function (i.e. immunometabolism) in immortalised mouse microglia (BV-2 cells) using the proinflammatory stimulus lipopolysaccharide (LPS) to induce general microglial activation. Microglial FABP4 expression was significantly increased following exposure to LPS, an outcome associated with a significant increase in microglial proliferation rate. LPS-stimulated BV-2 microglia demonstrated a significant increase in the production of reactive oxygen species (ROS) and tumour necrosis factor-alpha (TNF-α), phosphorylation of c-Jun N-terminal kinase (JNK), increased expression of Toll-like receptor 4 (TLR4), and reduced expression of uncoupling protein 2 (UCP2), all of which were reversed following FABP4 genetic silencing and chemical inhibition with BMS309403. The oxidation rate of 3H-oleic acid and microglial uptake of 3H-2-deoxy-D-glucose were modulated with LPS activation, processes which were restored with genetic and chemical inhibition of FABP4. This is the first study to report on the critical role of FABP4 in mediating the deleterious effects of LPS on microglial immunometabolism, suggesting that FABP4 may present as a novel therapeutic target to alleviate microglia-mediated neuroinflammation, a commonly reported factor in multiple neurodegenerative diseases. Graphical Abstract

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HIV-1 Tat drives the Fabp4/NF-κB feedback loop in microglia to mediate inflammatory response and neuronal apoptosis

Cited by 9 publications

References 41 publications

Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons

Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons

Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

Fatty Acid-Binding Protein 4 is Essential for the Inflammatory and Metabolic Response of Microglia to Lipopolysaccharide

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