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Monocyte phospholipase a2

Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
Chithra K Pushpan, Shalini V, Sindhu G, Parvathy Rathnam, Jayalekshmy A, Helen A
Atherosclerosis is a chronic inflammatory disease. The role of inflammation in atherosclerosis is well established, with all stages of disease progression being assessed as inflammatory response to injury. Preventive treatments and drugs identified so far are based on lipid lowering strategies which also involves functional foods and dietary supplementation. The present study investigated the effect of supplementation of Njavara rice bran oil (NjRBO), extracted from a medicinal rice variety, to high cholesterol diet (HCD) fed rats on atherosclerosis by attenuating the inflammatory responses in PBMCs, aortic endothelial cells and macrophages...
August 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jacob Barnes, Valeria Mondelli, Carmine M Pariante
This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case-control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2...
January 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Wei Hsum Yap, Nafees Ahmed, Yang Mooi Lim
Maslinic acid is a natural pentacyclic triterpenoid which has anti-inflammatory properties. A recent study showed that secretory phospholipase A2 (sPLA2) may be a potential binding target of maslinic acid. The human group IIA (hGIIA)-sPLA2 is found in human sera and their levels are correlated with severity of inflammation. This study aims to determine whether maslinic acid interacts with hGIIA-sPLA2 and inhibits inflammatory response induced by this enzyme. It is shown that maslinic acid enhanced intrinsic fluorescence of hGIIA-sPLA2 and inhibited its enzyme activity in a concentration-dependent manner...
October 2016: Lipids
Jie Chen, Hong-wen Cai, Jing Miao, Xiao-ming Xu, Wei Mao
OBJECTIVE: To observe the effects of Danlou Tablet (DT) on inflammatory reaction, and expressions of lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase A2 (sPLA2), and to analyze potential mechanisms. METHODS: Forty male Wistar rats were randomly and equally divided into five groups, i.e., the normal control group, the model group, the Western medicine (WM) group, the low dose DT group, the high dose DT group, 8 in each group. Rats in the normal control group were fed with basic forage for 12 successive weeks, while AS rat model was established in rats of the other four groups by feeding high fat and sugar forage plus intraperitoneal injection of vitamin D₃...
June 2016: Chinese Journal of Integrated Traditional and Western Medicine
Heng Boon Low, Chin Wen Png, Chunwei Li, De Yun Wang, Soon Boon Justin Wong, Yongliang Zhang
The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC) is a malignancy characterized by an intimate relationship between neoplastic cells and a non-neoplastic lymphoid component. Tumor-associated macrophages (TAMs) foster tumor progression through production of soluble mediators that support proliferation, angiogenesis, survival and invasion of malignant cells. However, the role of macrophages in the progression of NPC remains poorly understood. This study aims to investigate the functional and phenotypic changes that occur to macrophages in macrophage-NPC cell co-culture systems, and how these changes influence tumor cells...
August 1, 2016: Oncotarget
Markella V Zanni, Mabel Toribio, Gregory K Robbins, Tricia H Burdo, Michael T Lu, Amorina E Ishai, Meghan N Feldpausch, Amanda Martin, Kathy Melbourne, Virginia A Triant, Sujit Suchindran, Hang Lee, Udo Hoffmann, Kenneth C Williams, Ahmed Tawakol, Steven K Grinspoon
IMPORTANCE: Individuals with human immunodeficiency virus (HIV) infection receiving combined antiretroviral therapy (ART) have an increased risk of myocardial infarction. Effects of ART on arterial inflammation among treatment-naive individuals with HIV are unknown. OBJECTIVE: To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection. DESIGN, SETTING, PARTICIPANTS: Twelve treatment-naive HIV-infected individuals underwent fludeoxyglucose F 18 ([18F]-FDG) positron emission tomographic scanning for assessment of arterial inflammation, coronary computed tomographic angiography for assessment of subclinical atherosclerosis, and systemic immune and metabolic phenotyping before and 6 months after the initiation of therapy with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (combined ART)...
July 1, 2016: JAMA Cardiology
Benoit J Arsenault, Payal Kohli, Gilles Lambert, David A DeMicco, Rachel Laskey, Michael M Messig, John J P Kastelein, David D Waters
Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events...
August 15, 2016: American Journal of Cardiology
Laura Pertl, Sabine Kern, Martin Weger, Silke Hausberger, Markus Trieb, Vanessa Gasser-Steiner, Anton Haas, Hubert Scharnagl, Akos Heinemann, Gunther Marsche
PURPOSE: High-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients. METHODS: Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients...
2016: PloS One
K Otomo, O Amengual, Y Fujieda, H Nakagawa, M Kato, K Oku, T Horita, S Yasuda, M Matsumoto, K I Nakayama, S Hatakeyama, T Koike, T Atsumi
OBJECTIVE: The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by β2GPI-dependent anticardiolipin antibody (aCL/β2GPI) on monocytes. METHODS: Human serum incubated with FLAG-β2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed...
October 2016: Lupus
Munehiro Yamaguchi, Jennifer Zacharia, Tanya M Laidlaw, Barbara Balestrieri
Phospholipases A2 are enzymes that liberate membrane-bound lipids in a tissue and cell-specific fashion. Group V secretory phospholipase A2 is necessary for the development of M2 macrophages and their effector functions in a mouse model of the T-helper-2 allergic airway inflammation. However, the function of group V phospholipase A2 in human M2 activation and T-helper-2 inflammation is ill-defined. Transglutaminase-2, a protein cross-linking enzyme, is a newly identified marker of both human and mouse interleukin-4-activated M2 macrophages and is also found in the lungs of patients with asthma...
July 2016: Journal of Leukocyte Biology
Shiho Kanai, Keiichi Ishihara, Eri Kawashita, Toshiyuki Tomoo, Kazuhiro Nagahira, Yasuhiro Hayashi, Satoshi Akiba
We have previously shown that high-fat cholesterol diet (HFCD)-induced fatty liver and carbon tetrachloride (CCl4)-induced hepatic fibrosis are reduced in mice deficient in group IVA phospholipase A2 (IVA-PLA2), which plays a role in inflammation. We herein demonstrate the beneficial effects of ASB14780 (3-[1-(4-phenoxyphenyl)-3-(2-phenylethyl)-1H-indol-5-yl]propanoic acid 2-amino-2-(hydroxymethyl)propane-1,3-diol salt), an orally active IVA-PLA2 inhibitor, on the development of fatty liver and hepatic fibrosis in mice...
March 2016: Journal of Pharmacology and Experimental Therapeutics
Samuel Hernandez-Anzaldo, Evan Berry, Vesna Brglez, Dickson Leung, Tae Jin Yun, Jun Seong Lee, Janos G Filep, Zamaneh Kassiri, Cheolho Cheong, Gérard Lambeau, Richard Lehner, Carlos Fernandez-Patron
BACKGROUND: Endocrine functions of the heart have been well established. We investigated the hypothesis that cardiac secretion of a unique phospholipase A2 recently identified by our laboratory (cardiac secreted phospholipase A2 [sPLA2]) establishes a heart-liver endocrine axis that is negatively regulated by matrix metalloproteinase-2 (MMP-2). METHODS AND RESULTS: In Mmp2(-/-) mice, cardiac (but not hepatic) sPLA2 was elevated, leading to hepatic inflammation, immune cell infiltration, dysregulation of the sterol regulatory element binding protein-2 and liver X receptor-α pathways, abnormal transcriptional responses to dietary cholesterol, and elevated triglycerides in very low-density lipoprotein and in the liver...
November 13, 2015: Journal of the American Heart Association
Yongjun Guo, Bo Li, Xuejing Xu, Rong Wu, Weihua Li
BACKGROUND/AIMS: Group IIA secretory phospholipase A2 (sPLA2-IIA) has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. METHODS: Human aortic smooth muscle cells (HASMCs) were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP). Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL), sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002...
2015: Cellular Physiology and Biochemistry
Gabriella Passacquale, Paolo Di Giosia, Albert Ferro
Anti-inflammatory add-on therapy to conventional cardiovascular prophylaxis has been proposed as a novel therapeutic approach to potentially reduce residual cardiovascular risk. This hypothesis has been challenged by a series of unsuccessful Phase III studies testing the impact on clinical outcomes of novel agents with immunomodulatory actions. Specifically, the apparent ability of phospholipase A2 (PLA2) inhibitors and of antioxidants to ameliorate inflammation and to reduce coronary disease in Phase II trials did not translate into improved secondary cardiovascular prevention in larger population-based studies...
January 1, 2016: Cardiovascular Research
Xiaochun Tang, Gangqi Wang, Xingxing Liu, Xiaolei Han, Zhuang Li, Guangyao Ran, Zhanjun Li, Qi Song, Yuan Ji, Haijun Wang, Yuhui Wang, Hongsheng Ouyang, Daxin Pang
Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is associated with the risk of vascular disease. It circulates in human blood predominantly in association with low-density lipoprotein cholesterol (LDL-C) and hydrolyses oxidized phospholipids into pro-inflammatory products. However, in the mouse circulation, it predominantly binds to high-density lipoprotein cholesterol (HDL-C) and exhibits anti-inflammatory properties. To further investigate the effects of Lp-PLA2 in the circulation, we generated over-expressed Lp-PLA2 transgenic swine...
September 25, 2015: Biochemical and Biophysical Research Communications
Shun He, Benjamin G Chousterman, Ashley Fenn, Atsushi Anzai, Manfred Nairz, Martin Brandt, Ingo Hilgendorf, Yuan Sun, Yu-Xiang Ye, Yoshiko Iwamoto, Benoit Tricot, Ralph Weissleder, Colin Macphee, Peter Libby, Matthias Nahrendorf, Filip K Swirski
BACKGROUND: Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease...
September 2015: Circulation. Heart Failure
Li Jiao, Johannes Inhoffen, Hongying Gan-Schreier, Sabine Tuma-Kellner, Wolfgang Stremmel, Zhiwei Sun, Walee Chamulitrat
BACKGROUND: Inflammatory bowel disease results from a combination of dysfunction of intestinal epithelial barrier and dysregulation of mucosal immune system. iPLA2β has multiple homeostatic functions and shown to play a role in membrane remodeling, cell proliferation, monocyte chemotaxis, and apoptosis. The latter may render chronic inflammation and susceptibility for acute injury. AIMS: We aim to evaluate whether an inactivation of iPLA2β would enhance the pathogenesis of experimental colitis induced by dextran sodium sulfate...
December 2015: Digestive Diseases and Sciences
Simon McArthur, Thomas Gobbetti, Dennis H M Kusters, Christopher P Reutelingsperger, Roderick J Flower, Mauro Perretti
Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse as atherosclerosis and Alzheimer's disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by the protein annexin A1 (ANXA1), found in high abundance in inflammatory exudates. Using primary human blood monocytes from healthy donors, we identified ANXA1 as a potent CD14(+)CD16(-) monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed the p38 MAPK-mediated activation of a calcium independent phospholipase A2 with resultant synthesis of lysophosphatidic acid (LPA) driving chemotaxis through LPA receptor 2 and actin cytoskeletal mobilization...
August 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhuang Li, Wenzhi Ren, Xiaolei Han, Xingxing Liu, Gangqi Wang, Mingjun Zhang, Daxin Pang, Hongsheng Ouyang, Xiaochun Tang
SCOPE: ω3-polyunsaturated fatty acids (ω3-PUFAs) have beneficial effects on cardiovascular function, and lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with the risk of cardiovascular disease. Here, we investigated the effects of ω3-PUFAs on Lp-PLA2 expression in vitro and in vivo and explored the mechanisms involved. METHODS AND RESULTS: Human monocyticcells (THP-1) were induced into macrophages in an in vitro model. ω3-PUFAs suppressed Lp-PLA2 expression; the suppression induced by docosahexaenoic acid (DHA) was related to reduced inflammation...
September 2015: Molecular Nutrition & Food Research
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