Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

eLife, Journal Year: 2016, Volume and Issue: 5

Published: Feb. 19, 2016

Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate and reprogramming, the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts Akt-mTORC1 pathway regulate Acly, a key enzyme in Ac-CoA synthesis, leading increased histone acetylation M2 gene induction. Only subset genes controlled this way, including those regulating cellular proliferation chemokine production. Moreover, impinge on axis such activation. We propose calibrates state energetically demanding aspects which may define new role metabolism supporting

Language: Английский

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mTORC1 and mTORC2 in cancer and the tumor microenvironment

Oncogene, Journal Year: 2016, Volume and Issue: 36(16), P. 2191 - 2201

Published: Oct. 17, 2016

Language: Английский

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Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowthviatheir transfer into neurons

The FASEB Journal, Journal Year: 2017, Volume and Issue: 32(1), P. 512 - 528

Published: Sept. 21, 2017

Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after brain injury (TBI). Inhibiting excessive inflammatory response essential for improving outcome. To clarify regulatory mechanism microglial exosomes on neu-ronal in TBI, we focused studying impact exosomal miRNAs injured neurons this research. We used a repetitive (r)TBI mouse model harvested extracts from to phase TBI treat cultured BV2 microglia vitro. The were collected miRNA microarray analysis, which showed that expression level miR-124-3p increased most apparently miRNAs. found promoted anti-inflamed M2 polarization microglia, inhibited neuronal scratch-injured neurons. Further, mammalian target rapamycin (mTOR) signaling was implicated as being involved regulation by Gene Ontology Kyoto Encyclopedia Genes Genomes pathway analyses. Using mTOR activator MHY1485 confirmed inhibitory effect exerted suppressing activity signaling. PDE4B predicted be gene analysis. proved it directly targeted with luciferase reporter assay. overexpressed lentivirus transfection system, suggested suppressed mainly through inhibiting PDE4B. In addition, neurite outgrowth scratch injury, characterized an increase number branches total length, decreasedexpressiononRhoAand neurodegenerative proteins [Aß-peptide p-Tau]. It also improved outcome neuro-inflammation mice rTBI. Taken together, can inhibit contribute via their transfer into these effects targeting PDE4B, thus Therefore, could promising therapeutic interventions TBI. manipulated may provide novel therapy other diseases.—Huang, S., Ge, X., Yu, J., Han, Z., Yin, Li, Y., Chen, F., Wang, H., Zhang, Lei, P. Increased following inhibits contributes FASEB J. 32, 512-528 (2018). www.fasebj.org

Language: Английский

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Macrophage Polarization and Its Role in Liver Disease

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 14, 2021

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity polarization. Under pathological conditions, addition to the resident macrophages, other macrophages also recruited diseased tissues, polarize various phenotypes (mainly M1 M2) under stimulation of factors microenvironment, thus playing different roles functions. Liver diseases hepatic changes caused by a variety pathogenic (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic disease, metabolic-associated fatty fibrosis, hepatocellular carcinoma. Recent studies shown that macrophage polarization plays an role initiation development diseases. However, because both pathogenesis complex, mechanism need be further clarified. Therefore, origin mechanisms reviewed first this paper. It is found involves several molecular mechanisms, mainly TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, miRNA signaling pathways. In addition, paper expounds diseases, which aims provide references for research contributing therapeutic strategy ameliorating modulating

Language: Английский

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Mechanisms of Dupilumab

Clinical & Experimental Allergy, Journal Year: 2019, Volume and Issue: 50(1), P. 5 - 14

Published: Sept. 10, 2019

The Th2 cytokines interleukin 4 (IL-4) and IL-13 the heterodimeric IL-4 receptor (IL-4R) complexes that they interact with play a key role in pathogenesis of allergic disorders. Dupilumab is humanized IgG4 monoclonal antibody targets alpha chain (IL-4Rα), common to both IL-4R complexes: type 1 (IL-4Rα/γc; specific) 2 (IL-4Rα/IL-13Rα1; specific). In this review, we detail current state knowledge different signalling pathways coupled examine possible mechanisms action survey its clinical efficacy development widening spectrum applications relevant emphasis on precision medicine approaches blockade involved diseases.

Language: Английский

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