scholarly journals 4R-Cembranoid Treatment Alters Gene Expression of RAW264.7 Macrophages in Basal and Inflammatory Conditions

2020 ◽  
Author(s):  
Maxine N. Gonzalez-Vega ◽  
Sandeep sreerama ◽  
Kelvin Carrasquillo-Carrion ◽  
Abiel Roche-Lima ◽  
Susan Corey Best ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Parenchyma ◽  
Inflammatory Conditions ◽  
Raw264.7 Macrophages ◽  
Blood Brain Barrier Model ◽  
Peripheral Immune Response ◽  
Anti Inflammatory ◽  
Macrophage Adhesion ◽  
The Brain ◽  
Inflammatory Effect

Inflammation is considered an important target for stroke therapy because it induces secondary brain damage after the initial ischemic insult. Peripheral monocytes migrate to the brain parenchyma after a central insult. They then differentiate to macrophages in a positive feedback fashion contributing to damage instead of ischemic resolution and inflammation control. A cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R), decreases neurodegeneration after ischemia with central anti-inflammatory activity. This study aims to determine whether the central anti-inflammatory effect of 4R is effective against peripheral inflammation triggered by brain ischemia. To investigate the anti-inflammatory effect of 4R, we treated macrophages with lipopolysaccharide (LPS) as an inflammatory model, followed by treatment with 4R. Microarray transcriptome analysis of over 30,000 genes identified the differential expression of 393 genes. Genes related to inflammation, cell adhesion, and transcription were validated with qPCR, and reduced expression was determined. Quantification of NF-kB phosphorylation served as a marker for the modulation of inflammation through gene transcription. Our results show that 4R was associated with a reduction in NFKB1 and ITGB5 gene expression, increased phosphorylation of NF-kB, and a decrease in macrophage adhesion in a blood-brain barrier model. These results indicate that 4R can partially modulate the peripheral immune response, making 4R a potential drug against post-ischemic inflammation.

scholarly journals Inhibition of Inflammatory Response by Artepillin C in Activated RAW264.7 Macrophages

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ewelina Szliszka ◽  
Anna Mertas ◽  
Zenon P. Czuba ◽  
Wojciech Król
Keyword(s):  
Cell Viability ◽  
Radical Scavenging ◽  
Gm Csf ◽  
Raw264.7 Macrophages ◽  
Griess Reaction ◽  
Artepillin C ◽  
Anti Inflammatory ◽  
Radical Scavenging Ability ◽  
Brazilian Green Propolis ◽  
Inflammatory Effect

Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis. The aim of this study was to investigate the anti-inflammatory effect of artepillin C on LPS + IFN-γ- or PMA-stimulated RAW264.7 macrophages. The cell viability was evaluated by MTT and LDH assays. The radical scavenging ability was determined using DPPH•and ABTS•+. ROS and RNS generation was analyzed by chemiluminescence. NO concentration was detected by the Griess reaction. The release of various cytokines by activated RAW264.7 cells was measured in the culture supernatants using a multiplex bead array system based on xMAP technology. NF-κB activity was confirmed by the ELISA-based TransAM NF-κB kit. At the tested concentrations, the compound did not decrease the cell viability and did not cause the cytotoxicity. Artepillin C exerted strong antioxidant activity, significantly inhibited the production of ROS, RNS, NO, and cytokine IL-1β, IL-3, IL-4, IL-5, IL-9, IL-12p40, IL-13, IL-17, TNF-α, G-CSF, GM-CSF, MCP-1, MIP-1α, MIP-1β, RANTES, and KC, and markedly blocked NF-κB expression in stimulated RAW264.7 macrophages. Our findings provide new insights for understanding the mechanism involved in the anti-inflammatory effect of artepillin C and support the application of Brazilian green propolis in complementary and alternative medicine.

Heme oxygenase-1 mediates the anti-inflammatory effect of mushroom Phellinus linteus in LPS-stimulated RAW264.7 macrophages

2006 ◽  
Vol 106 (3) ◽  
pp. 364-371 ◽  
Author(s):  
Byung-Chul Kim ◽  
Joung-Woo Choi ◽  
Hye-Young Hong ◽  
Sin-Ae Lee ◽  
Suntaek Hong ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Phellinus Linteus ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Exosomal delivery of therapeutic modulators through the blood–brain barrier; promise and pitfalls

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morteza Heidarzadeh ◽  
Yasemin Gürsoy-Özdemir ◽  
Mehmet Kaya ◽  
Aysan Eslami Abriz ◽  
Amir Zarebkohan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Large Population ◽  
Drug Carriers ◽  
The Elderly ◽  
Brain Parenchyma ◽  
Main Question ◽  
Inflammatory Conditions ◽  
Degenerative Disorders ◽  
Delivery Strategies ◽  
The Brain

AbstractNowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50–100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.

scholarly journals PLA-PEG Nanoparticles Improve the Anti-Inflammatory Effect of Rosiglitazone on Macrophages by Enhancing Drug Uptake Compared to Free Rosiglitazone

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1845 ◽  
Author(s):  
Giovanna Giacalone ◽  
Nicolas Tsapis ◽  
Ludivine Mousnier ◽  
Hélène Chacun ◽  
Elias Fattal
Keyword(s):  
Polymeric Nanoparticles ◽  
Heart Diseases ◽  
The United States ◽  
Drug Uptake ◽  
Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Efficient Delivery ◽  
Anti Inflammatory ◽  
Atherosclerosis Treatment ◽  
Inflammatory Effect

Among cardiovascular diseases, atherosclerosis remains the first cause of death in the United States of America and Europe, as it leads to myocardial infarction or stroke. The high prevalence of heart diseases is due to the difficulty in diagnosing atherosclerosis, since it can develop for decades before symptoms occur, and to the complexity of the treatment since targets are also important components of the host defenses. The antidiabetics thiazolidinediones, among which is rosiglitazone (RSG), have demonstrated anti-atherosclerotic effect in animal models, and are therefore promising candidates for the improvement of atherosclerosis management. Nevertheless, their administration is hindered by the insurgence of severe side effects. To overcome this limitation, rosiglitazone has been encapsulated into polymeric nanoparticles, which permit efficient delivery to its nuclear target, and selective delivery to the site of action, allowing the reduction of unwanted effects. In the present work, we describe nanoparticle formulation using polylactic acid (PLA) coupled to polyethylene glycol (PEG), their characterization, and their behavior on RAW264.7 macrophages, an important target in atherosclerosis treatment. RSG nanocarriers showed no toxicity on cells at all concentrations tested, an anti-inflammatory effect in a dose-dependent manner, up to 5 times more efficient than the free molecule, and an increased RSG uptake which is consistent with the effect shown. These biodegradable nanoparticles represent a valid tool to be further investigated for the treatment of atherosclerosis.

scholarly journals Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently

2020 ◽  
Author(s):  
Ihsan Gadi ◽  
Sameen Fatima ◽  
Ahmed Elwakiel ◽  
Sumra Nazir ◽  
Mohd Mohanad Al-Dabet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Sterile Inflammation ◽  
Inflammasome Activation ◽  
Differential Effects ◽  
Anti Inflammatory ◽  
Anticoagulant Function ◽  
Inflammatory Effect

Rationale: While thrombin is the key protease in thrombus formation, other coagulation proteases, such as fXa or activated protein C (aPC), independently modulate intracellular signaling via partially distinct receptors. Objective: To study the differential effects of fXa or fIIa inhibition on gene expression and inflammation in myocardial ischemia-reperfusion injury (IRI). Methods and Results: Mice were treated with a direct fIIa inhibitor (fIIai) or direct fXa inhibitor (fXai) at doses that induced comparable anticoagulant effects ex vivo and in vivo (tail bleeding assay and FeCl3-induced thrombosis). Myocardial IRI was induced via LAD ligation. We determined infarct size and in vivo aPC generation, analyzed gene expression by RNAseq, and performed immunoblotting and ELISA. The signaling-only 3K3A-aPC variant and inhibitory antibodies that blocked all or only the anticoagulant function of aPC were used to determine the role of aPC. Doses of fIIai and fXai that induced comparable anticoagulant effects resulted in a comparable reduction in infarct size. However, unbiased gene expression analyses revealed marked differences, including pathways related to sterile inflammation and inflammasome regulation. fXai but not fIIai inhibited sterile inflammation by reducing the expression of proinflammatory cytokines (IL-1beta, IL-6, and TNFalpha) as well as NF-κB and inflammasome activation. This anti-inflammatory effect was associated with reduced myocardial fibrosis 28 days post myocardial IRI. Mechanistically, in vivo aPC generation was higher with fXai than with fIIai. Inhibition of the anticoagulant and signaling properties of aPC abolished the anti-inflammatory effect associated with fXai, while inhibiting only the anticoagulant function of aPC had no effect. Combining 3K3A-aPC with fIIai reduced the inflammatory response, mimicking the fXai-associated effect. Conclusions: We showed that specific inhibition of coagulation via DOACs had differential effects on gene expression and inflammation, despite comparable anticoagulant effects and infarct sizes. Targeting individual coagulation proteases induces specific cellular responses unrelated to their anticoagulant effect.

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