scholarly journals PI(3)P-p40 phox binding regulates NADPH oxidase activation in mouse macrophages and magnitude of inflammatory responses in vivo

2016 ◽  
Vol 101 (2) ◽  
pp. 449-457 ◽  
Author(s):  
Juhi Bagaitkar ◽  
Emilia A. Barbu ◽  
Lizet J. Perez-Zapata ◽  
Anthony Austin ◽  
Guangming Huang ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Inflammatory Responses ◽  
Mouse Macrophages ◽  
Nadph Oxidase Activation

scholarly journals Plant Extract of Limonium gmelinii Attenuates Oxidative Responses in Neurons, Astrocytes, and Cerebral Endothelial Cells In Vitro and Improves Motor Functions of Rats after Middle Cerebral Artery Occlusion

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1814
Author(s):  
Tulendy Nurkenov ◽  
Andrey Tsoy ◽  
Farkhad Olzhayev ◽  
Elvira Abzhanova ◽  
Anel Turgambayeva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Middle Cerebral Artery ◽  
Artery Occlusion ◽  
Ros Generation ◽  
Tnf Α ◽  
Cerebral Artery Occlusion ◽  
Nadph Oxidase Activation

There are numerous publications demonstrating that plant polyphenols can reduce oxidative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich source of polyphenols and other biologically active compounds. We have applied an oxidative and inflammatory model induced by NMDA, H2O2, and TNF-α in human primary neurons and astrocytes, and mouse cerebral endothelial cell (CECs) line in vitro. The levels of ROS generation, NADPH oxidase activation, P-selectin expression, and activity of ERK1/2 were evaluated by quantitative immunofluorescence analysis, confocal microscopy, and MAPK assay. In vivo, sensorimotor functions in rats with middle cerebral artery occlusion (MCAO) were assessed. In neurons NMDA induced overproduction of ROS, in astrocytes TNF-α initiated ROS generation, NADPH oxidase activation, and phosphorylation of ERK1/2. In CECs, the exposure by TNF-α induced oxidative stress and triggered the accumulation of P-selectin on the surface of the cells. In turn, pre-treatment of the cells with the extract of L. gmelinii suppressed oxidative stress in all cell types and pro-inflammatory responses in astrocytes and CECs. In vivo, the treatment with L. gmelinii extract improved motor activity in rats with MCAO.

scholarly journals miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses

2009 ◽  
Vol 106 (37) ◽  
pp. 15819-15824 ◽  
Author(s):  
Gang Liu ◽  
Arnaud Friggeri ◽  
Yanping Yang ◽  
Young-Jun Park ◽  
Yuko Tsuruta ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Negative Regulator ◽  
Microbial Pathogens ◽  
Cellular Activation ◽  
Mouse Macrophages ◽  
Non Coding Rnas ◽  
Maximal Induction

Toll-like receptors (TLRs) are major receptors that enable inflammatory cells to recognize invading microbial pathogens. MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes. In this study, we found that a microRNA, miR-147, was induced upon stimulation of multiple TLRs and functioned as a negative regulator of TLR-associated signaling events in murine macrophages. We first demonstrated that the NMES1 transcript was a functional primary miR-147. miR-147 was induced in LPS-stimulated mouse macrophages and under in vivo conditions in the lungs of LPS-treated mice. Expression of miR-147 was greater after cellular activation by TLR4 than after engagement of either TLR2 or TLR3, suggesting that maximal induction of miR-147 required activation of both NF-κB and IRF3. TLR4-induced miR-147 expression was both MyD88- and TRIF-dependent. The miR-147 promoter was responsive to TLR4 stimulation and both NF-κB and STAT1α bound to the miR-147 promoter. miR-147 mimics or induced expression of miR-147 decreased, whereas miR-147 knockdown increased inflammatory cytokine expression in macrophages stimulated with ligands to TLR2, TLR3, and TLR4. These data demonstrate a negative-feedback loop in which TLR stimulation induces miR-147 to prevent excessive inflammatory responses.

P5506Proprotein convertase subtilisin/kexin 9 (PCSK9) and lipopolysaccharide (LPS) in patients with atrial fibrillation. A biomarker post-hoc analysis from the ATHERO-AF cohort

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Pignatelli Spinazzola ◽  
A Farcomeni ◽  
D Pastori ◽  
F Violi
Keyword(s):  
Atrial Fibrillation ◽  
Nadph Oxidase ◽  
Rank Test ◽  
Post Hoc Analysis ◽  
Increased Risk ◽  
Post Hoc ◽  
First Time ◽  
Nadph Oxidase Activation

Abstract Background Proprotein convertase subtilisin/kexin 9 (PCSK9) and lipopolysaccharides (LPS) are emerging as novel risk factors for cardiovascular events (CVEs). In vitro evidence suggested that PCSK9 production may be elicited by LPS via oxidative stress, However, their relationship in patients with atrial fibrillation (AF) has not been investigated. Methods Post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular AF. At baseline, PCSK9, LPS and NADPH oxidase (sNOX2-dp) were measured. We also assessed adherence to Mediterranean Diet (Med-Diet). PCSK9 and LPS were correlated to incidence of CVEs. Results At multivariate analysis, with PCSK9 above the median as dependent variable we found that high adherence to Med-Diet and antiplatelet drugs were inversely correlated to PCSK9 (odds ratio [OR] 0.737 95% Confidence interval [CI] 0.643–0.845 p=0.001 and OR 0.437 95% CI 0.219–0.871 p=0.017 respectively), while sNOX2-dp and LPS concentrations (OR 1.759 C.I. 95% 1.167–2.650, p=0.007 and OR 1.727 C.I. 95% 1.147–2.600 p=0.009 respectively) were directly correlated. In particular use of oil and wine were negatively associated to high PCSK9 levels (OR 0.376 95% CI 0.185–0.763, p=0.001 and OR 0.460 95% CI 0.289–0.733 p=0.007, respectively). Patients with concomitant high PCSK9 and LPS (highest tertile for both) had and increased risk of CVEs as compared to those with low levels (lowest tertile for both) with 48 and 29 CVEs in each group respectively (Log-Rank test, p=0.022) Conclusion This study demonstrated for the first time in vivo that circulating levels of PCSK9 are associated with high LPS concentration and NADPH oxidase activation. Concomitant increase of PCSK9 and LPS increased the risk of CVEs.

scholarly journals Differential activation of RAGE by HMGB1 modulates neutrophil-associated NADPH oxidase activity and bacterial killing

2012 ◽  
Vol 302 (1) ◽  
pp. C249-C256 ◽  
Author(s):  
Jean-Marc Tadié ◽  
Hong-Beom Bae ◽  
Sami Banerjee ◽  
Jaroslaw W. Zmijewski ◽  
Edward Abraham
Keyword(s):  
Nadph Oxidase ◽  
Intraperitoneal Injection ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
High Mobility ◽  
Bacterial Killing ◽  
E Coli ◽  
Glycation End Products ◽  
Nadph Oxidase Activation

The receptor for advanced glycation end products (RAGE) plays an important role in host defense against bacterial infection. In the present experiments, we investigated the mechanisms by which RAGE contributes to the ability of neutrophils to eradicate bacteria. Wild-type ( RAGE+/+) neutrophils demonstrated significantly greater ability to kill Eschericia coli compared with RAGE−/−neutrophils. After intraperitoneal injection of E. coli , increased numbers of bacteria were found in the peritoneal fluid from RAGE−/−as compared with RAGE+/+mice. Exposure of neutrophils to the protypical RAGE ligand AGE resulted in activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and enhanced killing of E. coli , and intraperitoneal injection of AGE enhanced bacterial clearance during peritonitis. However, incubation of neutrophils with high mobility group box 1 protein (HMGB1), which also binds to RAGE, diminished E. coli -induced activation of NADPH oxidase in neutrophils and bacterial killing both in vitro and in vivo. Deletion of the COOH-terminal tail of HMGB1, a region necessary for binding to RAGE, abrogated the ability of HMGB1 to inhibit bacterial killing. Incubation of neutrophils with HMGB1 diminished bacterial or AGE-dependent activation of NADPH oxidase. The increase in phosphorylation of the p40phoxsubunit of NADPH oxidase that occurred after culture of neutrophils with E. coli was inhibited by exposure of the cells to HMGB1. These results showing that HMGB1, through RAGE-dependent mechanisms, diminishes bacterial killing by neutrophils as well as NADPH oxidase activation provide a novel mechanism by which HMGB1 can potentiate sepsis-associated organ dysfunction and mortality.

scholarly journals Carbon Monoxide-Releasing Molecule-2 Ameliorates Particulate Matter-Induced Aorta Inflammation via Toll-Like Receptor/NADPH Oxidase/ROS/NF-κB/IL-6 Inhibition

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Thi Thuy Tien Vo ◽  
Chien-Yi Hsu ◽  
Yinshen Wee ◽  
Yuh-Lien Chen ◽  
Hsin-Chung Cheng ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Particulate Matter ◽  
Nadph Oxidase ◽  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Air Pollutant ◽  
Matrix Metalloproteinase 2 ◽  
Beneficial Effects

Particulate matter (PM), a major air pollutant, may be associated with adverse cardiovascular effects. Reactive oxygen species- (ROS-) dependent proinflammatory cytokine production, such as interleukin-6 (IL-6), is a possible underlying mechanism. Carbon monoxide- (CO-) releasing molecule-2 (CORM-2) which liberates exogenous CO can exert many beneficial effects, particularly anti-inflammation and antioxidant effects. The purpose of this study was to explore the protective effects and underpinning mechanisms of CORM-2 on PM-induced aorta inflammation. Here, human aortic vascular smooth muscle cells (HASMCs) were utilized as in vitro models for the assessment of signaling pathways behind CORM-2 activities against PM-induced inflammatory responses, including Toll-like receptors (TLRs), NADPH oxidase, ROS, nuclear factor-kappa B (NF-κB), and IL-6. The modulation of monocyte adherence and HASMC migration, that are two critical cellular events of inflammatory process, along with their regulators, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) and MMP-9, in response to PM by CORM-2, were further evaluated. Finally, mice experiments under different conditions were conducted for the in vivo evaluation of CORM-2 benefits on the expression of inflammatory molecules including IL-6, ICAM-1, VCAM-1, MMP-2, and MMP-9. Our results found that PM could induce aorta inflammation in vitro and in vivo, as evidenced by the increase of IL-6 expression that was regulated by the TLR2 and TLR4/NADPH oxidase/ROS/NF-κB signaling pathway, thereby promoting ICAM-1- and VCAM-1-dependent monocyte adhesion and MMP-2- and MMP-9-dependent HASMC migration. Importantly, our experimental models demonstrated that CORM-2-liberated CO effectively inhibited the whole identified PM-induced inflammatory cascade in HASMCs and tissues. In conclusion, CORM-2 treatment may elicit multiple beneficial effects on inflammatory responses of aorta due to PM exposure, thereby providing therapeutic value in the context of inflammatory diseases of the cardiovascular system.

scholarly journals Characterization the binding of cytosolic phospholipase A2 alpha and NOX2 NADPH oxidase in mouse macrophages

2021 ◽  
Author(s):  
Yulia Solomonov ◽  
Nurit Hadad ◽  
Rachel Levy
Keyword(s):  
Amino Acids ◽  
Nadph Oxidase ◽  
Plasma Membranes ◽  
Superoxide Production ◽  
C2 Domain ◽  
Cytosolic Phospholipase ◽  
Px Domain ◽  
Mouse Macrophages ◽  
Nadph Oxidase Activation

Abstract Background: Previous studies have demonstrated that Cytosolic phospholipase A2a (cPLA2a) is absolutely required for NOX2 NADPH oxidase activation in human and mouse phagocytes. Moreover, upon stimulation, cPLA2a translocates to the plasma membranes of by binding to the assembled oxidase, forming a complex between its C2 domain and the PX domain of the oxidase cytosolic factor, p47phox in human phagocytes. Intravenous administration of an antisense against cPLA2a that significantly inhibited its expression in mouse peritoneal neutrophil and macrophages also inhibited superoxide production, in contrast to cPLA2a knockout mice that showed normal superoxide production. The aim of the present study was to determine whether there is a binding between cPLA2a-C2 domain and p47phox-PX in mouse macrophages, to further support the role of cPLA2a in oxidase regulation also in mouse phagocytes. Methods and Results: A significant binding of mouse GST-p47phox-PX domain fusion protein and cPLA2a in stimulated mouse phagocyte membranes was demonstrated by pull down experiments, although lower than that detected by human p47phox-PX domain. Substituting the amino acids Phe98, Asn99 and Gly100 to Cys98 Ser99 and Thr100 in mouse p47phox-PX domain (that are present in human p47phox-PX domain) caused strong binding that was similar to that detected by the human p47phox-PX domain. Conclusions: the binding between cPLA2a-C2 and p47phox-PX domains exist in mouse macrophages and is not unique to human phagocytes. The binding between the two proteins is lower in the mice probably due to the absence of amino acids Cys98 Ser99 and Thr100 in p47phox-PX domain that facilitate the binding to cPLA2a.

scholarly journals Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB

2021 ◽  
pp. 175342592110625
Author(s):  
Ning An ◽  
Tao Yang ◽  
Xiao-Xia Zhang ◽  
Mei-xia Xu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
In Vivo Studies ◽  
Lung Edema ◽  
Monocyte Chemoattractant Protein 1 ◽  
Mouse Macrophages ◽  
Anti Inflammatory ◽  
Pre Treatment

Acute lung injury (ALI) is associated with a high mortality due to inflammatory cell infiltration and lung edema. The development of ALI commonly involves the activation of NF-κB. Since bergamottin is a natural furanocoumarin showing the ability to inhibit the activation of NF-κB, in this study we aimed to determine the effect of bergamottin on ALI. RAW264.7 mouse macrophages were pre-treated with bergamottin and then stimulated with LPS. Macrophage inflammatory responses were examined. Bergamottin (50 mg/kg body mass) was intraperitoneally administrated to mice 12 h before injection of LPS, and the effect of bergamottin on LPS-induced ALI was evaluated. Our results showed that LPS exposure led to increased production of TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which was impaired by bergamottin pre-treatment. In vivo studies confirmed that bergamottin pre-treatment suppressed LPS-induced lung inflammation and edema and reduced the levels of pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluids. Mechanistically, bergamottin blocked LPS-induced activation of NF-κB signaling in lung tissues. Additionally, bergamottin treatment reduced NF-κB p65 protein acetylation, which was coupled with induction of SIRT1 expression. In conclusion, our results reveal the anti-inflammatory property of bergamottin in preventing ALI. Induction of SIRT1 and inhibition of NF-κB underlies the anti-inflammatory activity of bergamottin.

Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

2001 ◽  
Vol 86 (11) ◽  
pp. 1257-1263 ◽  
Author(s):  
Attilio Bondanza ◽  
Angelo Manfredi ◽  
Valérie Zimmermann ◽  
Matteo Iannacone ◽  
Angela Tincani ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Glycoprotein I ◽  
Activated Platelets ◽  
Tnf Α ◽  
Per Se ◽  
Antigen Presenting ◽  
Antiinflammatory Cytokine

SummaryScavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

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