記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

Background: Smoking increases the risk of atherothrombotic events. Tissue factor (TF) mainly expressed on monocytes plays an important role in thrombosis and atherosclerosis. Metabolic syndrome (MetS) is being increasingly recognized as a major atherothrombotic risk factor, but the effects of smoking on monocyte TF activity (MTFA), carotid atherosclerosis estimated on carotid intima-media thickness (CIMT), and long-term prognosis in MetS remain unclear. Methods and Results: A total of 301 MetS patients lacking any known cardiovascular disease were prospectively investigated and classified into 4 groups according to smoking status at entry and at 12 months as follows: never smokers, past smokers, quitters, and persistent smokers. Peripheral blood mononuclear cells (PBMC) were isolated, and MTFA was measured using a coagulation assay. Linear trends for higher baseline MTFA and CIMT were observed among persistent smokers, quitters, and past smokers compared with never smokers. At 12 months, MTFA and CIMT decreased in never and past smokers and quitters but increased in persistent smokers. Six acute myocardial infarctions and 8 strokes occurred during a median follow-up of 66.0 months. Persistent smoking was associated with an increased risk of events (P&lt
0.001). Conclusions: Smoking is associated with upregulated MTFA and progression of CIMT, which may be related to the risk of atherothrombotic events in MetS patients.

DOI： 10.1253/circj.CJ-17-0644

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN ATHEROSCLEROSIS SOC  

Aim: Malnutrition has been identified to be an independent predictor of morbidity and mortality in patients with chronic heart failure (CHF). However, the pathophysiological mechanisms underlying this pathway remain unclear.
Methods: Nutritional screening was performed using the controlling nutritional status (CONUT) score, which was calculated using the serum albumin and total cholesterol levels and lymphocyte number, in 114 CHF patients with a mean left ventricular ejection fraction of 26.6% +/- 6.4%. The carotid intima-media thickness (CIMT) is correlated with carotid atherosclerosis and is a significant predictor of future cardiovascular events. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-alpha was measured and expressed as mean +/- SD (pg/mL/10(6) PBMCs).
Results: A multivariate linear regression analysis showed that the production of monocyte TNF-alpha (beta coefficient = 0.434, p< 0.001) and mean CIMT (beta coefficient = 0.204, p= 0.006) were independent determinants of the CONUT score. During a median follow-up of 67.5 months, 45 patients experienced cardiac events, including 16 cardiac deaths and 29 readmissions for worsening CHF. A multivariate Cox hazard analysis demonstrated that a monocyte TNF-alpha level of >= 4.1 pg/mL/106 PBMCs (hazard ratio (HR), 14.10; 95% confidence interval (CI), 2.55-77.92; p = 0.002) and CONUT score of = 3 (HR, 11.97; 95% CI, 2.21-64.67; p = 0.004) were independently associated with the incidence of cardiac events.
Conclusions: These data indicate that a poor nutritional status as assessed using the CONUT score and atherosclerosis as indicated by CIMT is significantly associated with inflammation and predicts poor outcomes in patients with CHF.

DOI： 10.5551/jat.31526

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/JCP.0b013e318240a472

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT, INC  

S100A8 is implicated in the pathogenesis of inflammatory diseases. S100A8 is upregulated in macrophages by Toll-like receptors (TLR)-3, 4, and 9 agonists in an IL-10-dependent manner, and by corticosteroids in vitro and in vivo, and scavenges oxidants generated by activated phagocytes. Because if its elevated expression in various lung disorders, we asked whether S100A8 was protective in allergic inflammation. S100A8, but not Cys(41)-Ala S100A8, in which the single reactive Cys residue was replaced by Ala, reduced mast cell (MC) degranulation and production of particular cytokines (IL-6, IL-4, and granulocyte macrophage colony-stimulating factor) in response to IgE-crosslinking in vitro, likely by inhibiting intracellular reactive oxygen species production, thereby reducing downstream linker for activation of T cells and extracellular signal regulated kinase/mitogen-activated protein kinase phosphorylation. In lungs of mice with acute asthma, S100A8, but not Cys(41)-Ala S100A8, reduced MC degranulation, production of eosinophil chemoattractants (IL-5, eotaxin, and monocyte chemoattractant protein-1), and eosinophil infiltration. Suppression of IL-6 and IL-13 could have contributed to reduced mucus production seen in lungs of S100A8-treated mice. IgE production was unaffected. In asthma, there is an imbalance of anti-oxidant systems that are generally protective. Our results strongly support a protective role for S100A8 in allergic inflammation by modulating MC activation and eosinophil recruitment, and by scavenging oxidants generated by activated leukocytes, in processes reliant on its thiol-scavenging capacity. Antioxid. Redox Signal. 14, 1589-1600.

DOI： 10.1089/ars.2010.3583

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

UVB irradiation modulates immune responses in the skin and is a major cause of sunburn, during which neutrophils accumulate in the skin. Because of their abundance in skin and ability to produce a variety of proinflammatory mediators, we propose that mast cells may play a key role in ultraviolet B (UVB)-induced skin inflammation. Cord blood-derived human mast cells were treated in vitro with varying doses of UVB and production of multiple cytokines was measured in culture supernatants. UVB exposure significantly increased the release of interleukin (IL)-8 and modestly increased IL-1 alpha production, but cytokines such as IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were unaffected. Cycloheximide reduced the UVB-mediated induction of IL-8 by 30-40%, suggesting that new protein synthesis contributed to IL-8 production. In line with this, UVB treatment of mast cells significantly increased IL-8 mRNA. In contrast to its effect on IL-8 production, optimal doses of UVB did not provoke histamine or tryptase release, indicating little effect on degranulation. Our data suggest that mast cells may play a major role during UVB-induced acute inflammation by selectively inducing cytokines involved in neutrophil recruitment.

DOI： 10.1111/j.1365-2249.2007.03332.x

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