scholarly journals Butanolic Extract of Noni Inhibits Proliferation, Inflammation, and Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Expression in Cultured Smooth Muscle Cells

2020 ◽  
Vol 15 (6) ◽  
pp. 1934578X2093203
Author(s):  
Takanori Matsui ◽  
Yuji Ishibashi ◽  
Ami Sotokawauchi ◽  
Fumiyuki Isami ◽  
Yumi Abe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Intercellular Adhesion Molecule ◽  
Ros Generation ◽  
Atherosclerotic Cardiovascular Disease ◽  
Proprotein Convertase ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Reactions ◽  
Monocyte Chemoattractant Protein 1 ◽  
Butanolic Extract ◽  
Gene And Protein Expression

Platelet-derived growth factor-BB (PDGF-BB) plays a central role in smooth muscle cell (SMC) proliferation and inflammation, being involved in atherosclerotic cardiovascular disease. We have previously found that butanolic extract of noni, a tropical plant belonging to the family Rubiaceae, exerts anti-inflammatory effects on endothelial cells exposed to advanced glycation end products (AGEs). Here, we examined the effects of noni extract on oxidative stress production, growth, and inflammatory reactions in PDGF-BB or AGE-exposed SMCs. Reactive oxygen species (ROS) generation, cell proliferation, and adhesion were measured by a fluorescent dye, a colorimetric agent, and labeled THP-1 cells, respectively. Gene and protein expression was evaluated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. Butanolic extract of noni reduced ROS production, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and proprotein convertase subtilisin kexin type 9 (PCSK9) expression, and proliferation in, and THP-1 cell adhesion to, PDGF-BB-exposed SMCs. Gene expression and protein level of receptor for AGEs (RAGE) were significantly decreased by noni extract in SMCs. Furthermore, AGEs significantly increased PCSK9 mRNA and protein levels in SMCs, which were inhibited by noni extract or an antioxidant N-acetylcysteine. Our present study suggests that butanolic extract of noni not only inhibits the PDGF-BB-induced proliferation and inflammatory reactions in SMCs through its antioxidative properties but also reduces PCSK9 levels in AGE-exposed SMCs via suppression of RAGE expression. Butanolic extract of noni may play a protective role against atherosclerosis.

scholarly journals Insulin Inhibits Intranuclear Nuclear Factor κB and Stimulates IκB in Mononuclear Cells in Obese Subjects: Evidence for an Anti-inflammatory Effect?

2001 ◽  
Vol 86 (7) ◽  
pp. 3257-3265 ◽  
Author(s):  
Paresh Dandona ◽  
Ahmad Aljada ◽  
Priya Mohanty ◽  
Husam Ghanim ◽  
Wael Hamouda ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Plasminogen Activator Inhibitor ◽  
Intercellular Adhesion Molecule ◽  
Ros Generation ◽  
Intercellular Adhesion Molecule 1 ◽  
Plasminogen Activator Inhibitor 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Anti Inflammatory ◽  
Pai 1 ◽  
Inflammatory Effect

In view of the fact that insulin resistance is associated with atherogenesis and that troglitazone, an insulin sensitizer, has anti-inflammatory effects, which may be potentially antiatherogenic in the long term, we have now investigated whether insulin has potential anti-inflammatory effects. We infused 2.0 to 2.5 IU/h in 5% dextrose (100 mL/h) iv into 10 obese subjects for 4 h followed by 5% dextrose alone for 2 h. The rate of insulin infusion was varied to maintain glucose concentrations as close to the baseline as possible. Blood samples were obtained before and at 2, 4, and 6 h. Subjects were also infused with 5% dextrose without insulin and with saline on separate occasions. Intranuclear nuclear factor κB (NFκB) in mononuclear cells fell at 2 and further at 4 h, reverting toward the baseline at 6 h (P < 0.05). IκB increased significantly at 2 h, increasing further at 4 h and remaining elevated at 6 h (P < 0.001). Reactive oxygen species (ROS) generation by mononuclear cells fell significantly at 2 h and fell further at 4 h; it partially reverted to baseline at 6 h (P < 0.005). p47phox subunit, the key protein of nicotinamide adenine dinucleotide phosphate oxidase also fell at 2 h and 4 h, reverting toward the baseline at 6 h (P < 0.05). In addition, soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) fell significantly following insulin infusion. Glucose or saline infusions without insulin caused no alteration in NFκB, IκB, ROS generation, p47phox subunit, sICAM-1, MCP-1, or PAI-1. We conclude that insulin has a potent acute anti-inflammatory effect including a reduction in intranuclear NFκB, an increase in IκB, and decreases in ROS generation, p47phox subunit, plasma soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1. This acute anti-inflammatory effect, if demonstrated in the long term, may have implications for atherosclerosis and its complications.

Neutrophil-dependent augmentation of PAF-induced vasoconstriction and albumin flux in coronary arterioles

1998 ◽  
Vol 275 (4) ◽  
pp. H1138-H1147 ◽  
Author(s):  
Qiaobing Huang ◽  
Mac Wu ◽  
Cynthia Meininger ◽  
Katherine Kelly ◽  
Yuan Yuan
Keyword(s):  
Platelet Activating Factor ◽  
Microvascular Dysfunction ◽  
Low Flow ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Apparent Permeability ◽  
Inflammatory Reactions ◽  
Coronary Arterioles ◽  
Flow Velocities

Platelet-activating factor (PAF) has been implicated in the pathogenesis of ischemic heart disease, reperfusion injury, and inflammatory reactions. Although neutrophils have been shown to primarily mediate PAF-induced microvascular dysfunction, the vasoactive effect of PAF and its neutrophil-dependent mechanism have not been directly and systematically studied in coronary resistance vessels. Therefore, the aim of this study was to examine the effects of PAF on coronary arteriolar function and neutrophil dynamics using an isolated and perfused microvessel preparation. Topical application of PAF to the vessels induced a dose-dependent decrease in the diameter but an increase in the apparent permeability coefficient of albumin. Disruption of the endothelium abolished the vasomotor response to PAF, and perfusion of neutrophils significantly augmented PAF-induced changes in vasomotor tone and permeability. Furthermore, the interaction between neutrophils and the endothelium was studied in the intact perfused coronary arterioles. Under control conditions, there were no adherent neutrophils observed in the vessels at varied intraluminal flow velocities. However, administration of PAF caused neutrophil adhesion to the endothelium of coronary arterioles at low flow velocities. Western blot analysis indicated that PAF upregulated the expression of intercellular adhesion molecule-1 in cultured coronary microvascular endothelial cells. Taken together, the results suggest that 1) PAF induces vasoconstriction and hyperpermeability in coronary arterioles via an endothelium-dependent and neutrophil-mediated mechanism, and 2) PAF is able to stimulate neutrophil adhesion in coronary arterioles under a condition of low flow rate.

Intrinsic ICAM-1/LFA-1 activation mediates altered responsiveness of atopic asthmatic airway smooth muscle

2000 ◽  
Vol 278 (6) ◽  
pp. L1154-L1163 ◽  
Author(s):  
Michael M. Grunstein ◽  
Hakon Hakonarson ◽  
Neil Maskeri ◽  
Cecilia Kim ◽  
Sing Chuang
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Constitutive Expression ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Blocking Antibody ◽  
Asthmatic Patients

Cell adhesion molecules (CAMs) have been importantly implicated in the pathobiology of the airway responses in allergic asthma, including inflammatory cell recruitment into the lungs and altered bronchial responsiveness. To elucidate the mechanism of CAM-related mediation of altered airway responsiveness in the atopic asthmatic state, the expressions and actions of intercellular adhesion molecule-1 (ICAM-1) and its counterreceptor ligand lymphocyte function-associated antigen-1 (LFA-1; i.e., CD11a/CD18) were examined in isolated rabbit airway smooth muscle (ASM) tissues and cultured human ASM cells passively sensitized with sera from atopic asthmatic patients or nonatopic nonasthmatic (control) subjects. Relative to control tissues, the atopic asthmatic sensitized ASM exhibited significantly enhanced maximal contractility to acetylcholine and attenuated relaxation responses to isoproterenol. These proasthmatic changes in agonist responsiveness were ablated by pretreating the atopic sensitized tissues with a monoclonal blocking antibody (MAb) to either ICAM-1 or CD11a, whereas a MAb directed against the related β2-integrin Mac-1 had no effect. Moreover, relative to control tissues, atopic asthmatic sensitized ASM cells displayed an autologously upregulated mRNA and cell surface expression of ICAM-1, whereas constitutive expression of CD11a was unaltered. Extended studies further demonstrated that 1) the enhanced expression and release of soluble ICAM-1 by atopic sensitized ASM cells was prevented when cells were pretreated with an interleukin (IL)-5-receptor-α blocking antibody and 2) administration of exogenous IL-5 to naive (nonsensitized) ASM cells induced a pronounced soluble ICAM-1 release from the cells. Collectively, these observations provide new evidence demonstrating that activation of the CAM counterreceptor ligands ICAM-1 and LFA-1, both of which are endogenously expressed in ASM cells, elicits autologously upregulated IL-5 release and associated changes in ICAM-1 expression and agonist responsiveness in atopic asthmatic sensitized ASM.

scholarly journals Osteopontin Predicts Three-Month Outcome in Stroke Patients Treated by Reperfusion Therapies

2020 ◽  
Vol 9 (12) ◽  
pp. 4028
Author(s):  
Elena Meseguer ◽  
Devy Diallo ◽  
Julien Labreuche ◽  
Hugo Charles ◽  
Sandrine Delbosc ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Tissue Remodeling ◽  
Intercellular Adhesion Molecule ◽  
Cathepsin S ◽  
Intercellular Adhesion Molecule 1 ◽  
Stroke Patients ◽  
Monocyte Chemoattractant Protein 1 ◽  
Significance Level ◽  
Matrix Metallopeptidase

Establishing a prognosis at hospital admission after stroke is a major challenge. Inflammatory processes, hemostasis, vascular injury, and tissue remodeling are all involved in the early response to stroke. This study analyzes whether 22 selected biomarkers, sampled at admission, predict clinical outcomes in 153 stroke patients treated by thrombolysis and mechanical endovascular treatment (MET). Biomarkers were related to hemostasis (u-plasminogen activator/urokinase (uPA/urokinase), serpin E1/PAI-1, serpin C1/antithrombin-III, kallikrein 6/neurosin, alpha 2-macroglobulin), inflammation[myloperoxidase (MPO), chemokine ligand 2/monocyte chemoattractant protein-1 chemokine (CCL2/MCP-1), adiponectin, resistin, cell-free DNA (cDNA), CD40 Ligand (CD40L)], endothelium activation (Vascular cell adhesion protein 1 (VCAM-1) intercellular adhesion molecule 1 (ICAM-1), platelet endothelial cell adhesion molecule 1 (CD31/PECAM-1)], and tissue remodeling (total cathepsin S, osteopontin, cystatin C, neuropilin-1, matrix metallopeptidase 2 (MMP-2), matrix metallopeptidase 3 (MMP-3), matrix metallopeptidase 9 (MMP-9), matrix metallopeptidase 13 (MMP-13)]. Correlations between their levels and excellent neurological improvement (ENI) at 24 h and good outcomes (mRS 0–2) at three months were tested. Osteopontin and favorable outcomes reached the significance level (p = 0.008); the adjusted OR per SD increase in log-transformed osteopontin was 0.34 (95%CI, 0.18–0.62). The relationship between total cathepsin S and MPO with ENI, was borderline of significance (p = 0.064); the adjusted OR per SD increase in log-transformed of total cathepsin S and MPO was 0.54 (95%CI, 0.35–0.81) and 0.51 (95%CI, 0.32–0.80), respectively. In conclusion, osteopontin levels predicted three-month favorable outcomes, supporting the use of this biomarker as a complement of clinical and radiological parameters for predicting stroke prognosis.

scholarly journals Lipopolysaccharide induces ICAM-1 expression via a c-Src/NADPH oxidase/ROS-dependent NF-κB pathway in human pulmonary alveolar epithelial cells

2016 ◽  
Vol 310 (7) ◽  
pp. L639-L657 ◽  
Author(s):  
Rou-Ling Cho ◽  
Chien-Chung Yang ◽  
I-Ta Lee ◽  
Chih-Chung Lin ◽  
Pei-Ling Chi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nadph Oxidase ◽  
Adhesion Molecule ◽  
Alveolar Epithelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Ros Generation ◽  
Intercellular Adhesion Molecule 1 ◽  
Mapk Activation ◽  
Promoter Assay ◽  
Alveolar Epithelial

Upregulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Lipopolysaccharide (LPS) has been shown to play a key role in inflammation via adhesion molecule induction and then causes lung injury. However, the mechanisms underlying LPS-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. We showed that LPS induced ICAM-1 expression in HPAEpiCs, revealed by Western blotting, RT-PCR, real-time PCR, and promoter assay. Pretreatment with the inhibitor of c-Src (protein phosphatase-1, PP1), reactive oxygen species (ROS) (Edaravone), NADPH oxidase (apocynin and diphenyleneiodonium chloride), EGFR (AG1478), PDGFR (AG1296), phosphatidylinositol-3-kinase (PI3K) (LY294002), MEK1/2 (U0126), or NF-κB (Bay11-7082) and transfection with siRNAs of c-Src, EGFR, PDGFR, Akt, p47 phox, Nox2, Nox4, p42, and p65 markedly reduced LPS-induced ICAM-1 expression and monocyte adherence to HPAEpiCs challenged with LPS. In addition, we established that LPS stimulated phosphorylation of c-Src, EGFR, PDGFR, Akt, or p65, which was inhibited by pretreatment with their respective inhibitors. LPS induced Toll-like receptor 4 (TLR4), MyD88, TNF receptor-associated factor 6 (TRAF6), c-Src, p47 phox, and Rac1 complex formation 2, which was attenuated by transfection with c-Src or TRAF6 siRNA. Furthermore, LPS markedly enhanced NADPH oxidase activation and intracellular ROS generation, which were inhibited by PP1. We established that LPS induced p42/p44 MAPK activation via a c-Src/NADPH oxidase/ROS/EGFR, PDGFR/PI3K/Akt-dependent pathway in these cells. Finally, we observed that LPS significantly enhanced NF-κB and IκBα phosphorylation, NF-κB translocation, and NF-κB promoter activity, which were inhibited by PP1, Edaravone, apocynin, diphenyleneiodonium chloride, AG1478, AG1296, LY294002 , or U0126. These results demonstrated that LPS induces p42/p44 MAPK activation mediated through the TLR4/MyD88/TRAF6/c-Src/NADPH oxidase/ROS/EGFR, PDGFR/PI3K/Akt pathway, which in turn initiates the activation of NF-κB and ultimately induces ICAM-1 expression in HPAEpiCs.

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