Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression

Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resembling the crosstalk between macrophages and glioblastoma cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) and M2 (mediate anti-inflammatory function) macrophages, converting M1 into TAMs and augmenting pro-tumor functions of M2 macrophages. In turn, these GBex-reprogrammed TAMs, produce exosomes decorated by immunosuppressive and tumor-growth promoting proteins. TAM-derived exosomes disseminate these proteins in the tumor microenvironment (TME) promoting tumor cell migration and proliferation. Mechanisms underlying the promotion of glioblastoma growth involved Arginase-1+ exosomes produced by the reprogrammed TAMs. A selective Arginase-1 inhibitor, nor-NOHA reversed growth-promoting effects of Arginase-1 carried by TAM-derived exosomes. The data suggest that GBex-reprogrammed Arginase-1+ TAMs emerge as a major source of exosomes promoting tumor growth and as a potential therapeutic target in glioblastoma.

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An in vitro model of human bronchial epithelial cells for the investigation of the role of the airway epithelium in asthma exacerbations

Pneumologie ◽

10.1055/s-0037-1619393 ◽

2018 ◽

Vol 72 (S 01) ◽

pp. S101-S102

Author(s):

JC Ehlers ◽

S Bartel ◽

C Vock ◽

H Fehrenbach

Keyword(s):

Epithelial Cells ◽

Airway Epithelium ◽

In Vitro Model ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Asthma Exacerbations ◽

Vitro Model

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Homeopathic potencies of Arnica montana L. change gene expression in a Tamm-Horsfall protein-1 cell line in vitro model: the role of ethanol as a possible confounder and statistical bias

Journal of Integrative Medicine ◽

10.1016/s2095-4964(17)60346-7 ◽

2017 ◽

Vol 15 (4) ◽

pp. 255-264 ◽

Cited By ~ 4

Author(s):

Salvatore Chirumbolo ◽

Geir Bjørklund

Keyword(s):

Gene Expression ◽

Cell Line ◽

In Vitro Model ◽

Statistical Bias ◽

Arnica Montana ◽

Vitro Model

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A Role of Intravenous Immunoglobulin in Human Parechovirus Type 3 Infection in an In Vitro Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw172.20 ◽

2016 ◽

Vol 3 (suppl_1) ◽

Cited By ~ 2

Author(s):

Ryohei Izumita ◽

Yuta Aizawa ◽

Kanako Watanabe ◽

Akihiko Saitoh

Keyword(s):

Intravenous Immunoglobulin ◽

In Vitro Model ◽

Human Parechovirus ◽

Vitro Model ◽

Type 3

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The pivotal role of micro-environmental cells in a human blood–brain barrier in vitro model of cerebral ischemia: functional and transcriptomic analysis

Fluids and Barriers of the CNS ◽

10.1186/s12987-020-00179-3 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Anna Gerhartl ◽

Nadja Pracser ◽

Alexandra Vladetic ◽

Sabrina Hendrikx ◽

Heinz-Peter Friedl ◽

...

Keyword(s):

Cerebral Ischemia ◽

Blood Brain Barrier ◽

Human Blood ◽

In Vitro Model ◽

Transcriptomic Analysis ◽

Pivotal Role ◽

Brain Barrier ◽

Vitro Model

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An In Vitro Model for Determining Tumor Cell Migration Under Metabolic Gradients

Advances in Experimental Medicine and Biology - Oxygen Transport to Tissue XL ◽

10.1007/978-3-319-91287-5_32 ◽

2018 ◽

pp. 201-205 ◽

Cited By ~ 2

Author(s):

Yusuke Tsuruno ◽

Kaima Okubo ◽

Takahiro Fujiwara ◽

Yoshihisa Yamaoka ◽

Eiji Takahashi

Keyword(s):

Cell Migration ◽

Tumor Cell ◽

In Vitro Model ◽

Tumor Cell Migration ◽

Vitro Model

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β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21113955 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3955

Author(s):

Jesus Fernandez-Abascal ◽

Elda Chiaino ◽

Maria Frosini ◽

Gavin P. Davey ◽

Massimo Valoti

Keyword(s):

Complex I ◽

In Vitro Model ◽

Inhibitory Effects ◽

Cyp Induction ◽

Cyp Isoforms ◽

Vitro Model ◽

Complex I Activity ◽

Cyp 2D6

The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis.

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2-Hydroxy-(4-methylseleno)butanoic Acid Is Used by Intestinal Caco-2 Cells as a Source of Selenium and Protects against Oxidative Stress

Journal of Nutrition ◽

10.1093/jn/nxz190 ◽

2019 ◽

Vol 149 (12) ◽

pp. 2191-2198

Author(s):

Joan Campo-Sabariz ◽

David Moral-Anter ◽

M Teresa Brufau ◽

Mickael Briens ◽

Eric Pinloche ◽

...

Keyword(s):

Oxidative Stress ◽

In Vitro Model ◽

Thioredoxin Reductase ◽

Protein Carbonyl ◽

Butanoic Acid ◽

H2o2 Treatment ◽

Vitro Model ◽

Gpx Activity

ABSTRACT Background Selenium (Se) participates in different functions in humans and other animals through its incorporation into selenoproteins as selenocysteine. Inadequate dietary Se is considered a risk factor for several chronic diseases associated with oxidative stress. Objective The role of 2-hydroxy-(4-methylseleno)butanoic acid (HMSeBA), an organic form of Se used in animal nutrition, in supporting selenoprotein synthesis and protecting against oxidative stress was investigated in an in vitro model of intestinal Caco-2 cells. Methods Glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD) activities, selenoprotein P1 protein (SELENOP) and gene (SELENOP) expression, and GPX1 and GPX2 gene expression were studied in Se-deprived (FBS removal) and further HMSeBA-supplemented (0.1–625 μM, 72 h) cultures. The effect of HMSeBA supplementation (12.5 and 625 μM, 24 h) on oxidative stress induced by H2O2 (1 mM) was evaluated by the production of reactive oxygen species (ROS), 4-hydroxy-2-nonenal (4-HNE) adducts, and protein carbonyl residues compared with a sodium selenite control (SS, 5 μM). Results Se deprivation induced a reduction (P < 0.05) in GPX activity (62%), GPX1 expression, and both SELENOP (33%) and SELENOP expression. In contrast, an increase (P < 0.05) in GPX2 expression and no effect in TXNRD activity (P = 0.09) were observed. HMSeBA supplementation increased (P < 0.05) GPX activity (12.5–625 μM, 1.68–1.82-fold) and SELENOP protein expression (250 and 625 μM, 1.87- and 2.04-fold). Moreover, HMSeBA supplementation increased (P < 0.05) GPX1 (12.5 and 625 μM), GPX2 (625 μM), and SELENOP (12.5 and 625 μM) expression. HMSeBA (625 μM) was capable of decreasing (P < 0.05) ROS (32%), 4-HNE adduct (49%), and protein carbonyl residue (75%) production after H2O2 treatment. Conclusion Caco-2 cells can use HMSeBA as an Se source for selenoprotein synthesis, resulting in protection against oxidative stress.

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