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Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Eleonora Cianci, Oriana Trubiani, Francesca Diomede, Ilaria Merciaro, Ida Meschini, Pantaleone Bruni, Fausto Croce, Mario Romano
Lipoxin (LX)A4 is a lipoxygenase-formed arachidonic acid metabolite with potent anti-inflammatory, pro-resolution properties. Its therapeutic efficacy has been largely demonstrated in a variety of cellular, preclinical and clinical models. Among these, periodontal disease, where LXA4 promotes tissue repair, also by modulating functions of human periodontal ligament stem cells (hPDLSCs). As medicated biomembranes may be particularly useful in clinical settings, where local stimulation of tissue repair is needed, we used electrospinning to embed LXA4 in membranes made of poly(ethylene oxide) (PEO) and poly(d,l-lactide) (PDLLA)...
October 11, 2016: International Journal of Pharmaceutics
Hao Wu, Ana R Rodriguez, Bernd W Spur, Venkat Venkataraman
A low-cost, easy-to-use and powerful model system is established to evaluate potential treatments that could ameliorate blood retinal barrier breach. An inflammatory factor, histamine, is demonstrated to compromise vessel integrity in the cultured retina through positive staining of IgG outside of the blood vessels. The effects of histamine itself and those of candidate drugs for potential treatments, such as lipoxin A4, are assessed using three parameters: blood vessel leakage via IgG immunostaining, activation of Müller cells via GFAP staining and change in neuronal dendrites through staining for MAP2...
2016: Journal of Visualized Experiments: JoVE
Jayashree A Chandrasekharan, Xiao M Huang, Alexandar Hwang, Neelam Sharma-Walia
: Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's Sarcoma (KS) and Primary Effusion Lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins...
September 28, 2016: Journal of Virology
Qiansheng Huang, Yajie Chen, Qionghua Chen, Huanteng Zhang, Yi Lin, Maobi Zhu, Sijun Dong
Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure-activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model...
September 23, 2016: Archives of Toxicology
Esther Titos, Bibiana Rius, Cristina López-Vicario, José Alcaraz-Quiles, Verónica García-Alonso, Aritz Lopategi, Jesmond Dalli, Juan José Lozano, Vicente Arroyo, Salvadora Delgado, Charles N Serhan, Joan Clària
Persistent activation of the innate immune system greatly influences the risk for developing metabolic complications associated with obesity. In this study, we explored the therapeutic potential of the specialized proresolving mediator (SPM) resolvin D1 (RvD1) to actively promote the resolution of inflammation in human visceral adipose tissue from obese (Ob) patients. Using liquid chromatography-tandem mass spectrometry-based metabololipidomic analysis, we identified unbalanced production of SPMs (i.e., D- and E-series resolvins, protectin D1, maresin 1, and lipoxins) with respect to inflammatory lipid mediators (i...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Gopalan Narendran, Dhanasekaran Kavitha, Ramesh Karunaianantham, Leonardo Gil-Santana, Jilson L Almeida-Junior, Sirasanambatti Devarajulu Reddy, Marimuthu Makesh Kumar, Haribabu Hemalatha, Nagesh Nalini Jayanthi, Narayanan Ravichandran, Raja Krishnaraja, Angamuthu Prabhakar, Tamizhselvan Manoharan, Lokeswaran Nithyananthan, Gunasundari Arjunan, Mohan Natrajan, Soumya Swaminathan, Bruno B Andrade
BACKGROUND: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory phenomenon complicating HIV management in coincidental tuberculosis (TB) infection, upon immune reconstitution driven by antiretroviral therapy (ART). Leukotriene A4 hydroxylase (LTA4H), an enzyme which converts LTA4 to LTB4, regulates the balance between the anti-inflammatory lipoxins and pro-inflammatory LTB4, with direct implications in TB-driven inflammation. In humans, a single nucleotide polymorphism (SNP) in the LTA4H promoter which regulates its transcriptional activity (rs17525495) has been identified and described to impact clinical severity of TB presentation and response to corticosteroid therapy...
2016: PloS One
Anju Singh, Tabassum Rahman, Rose Bartiss, Alireza Arabshahi, Jeevan Prasain, Stephen Barnes, Florin Marcel Musteata, Timothy J Sellati
Respiratory infection with Francisella tularensis (Ft) is characterized by a muted, acute host response, followed by sepsis-like syndrome that results in death. Infection with Ft establishes a principally anti-inflammatory environment that subverts host-cell death programs to facilitate pathogen replication. Although the role of cytokines has been explored extensively, the role of eicosanoids in tularemia pathogenesis is not fully understood. Given that lipoxin A4 (LXA4) has anti-inflammatory properties, we investigated whether this lipid mediator affects host responses manifested early during infection...
September 14, 2016: Journal of Leukocyte Biology
R L Simões, N M De-Brito, H Cunha-Costa, V Morandi, I M Fierro, I M Roitt, C Barja-Fidalgo
In tumor microenvironments, the macrophage population is heterogeneous, but some macrophages can acquire tumor-promoting characteristics. These tumor-associated macrophages (TAM) exhibit an M2-like profile, with deficient production of NO and ROS, characteristics of pro-inflammatory M1 cytotoxic macrophages. Lipoxins (LX) and 15-epi-lipoxins are lipid mediators which can induce certain features of M2 macrophages in mononuclear cells, but their effects on TAM remain to be elucidated. This study tested the hypothesis that ATL-1, a synthetic analogue of 15-epi-lipoxin A4 , could modulate TAM activity profile...
September 12, 2016: International Journal of Cancer. Journal International du Cancer
Anna Polus, Barbara Zapala, Urszula Razny, Anna Gielicz, Beata Kiec-Wilk, Malgorzata Malczewska-Malec, Marek Sanak, Caroline E Childs, Philip C Calder, Aldona Dembinska-Kiec
The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8g EPA+DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured...
August 12, 2016: Biochimica et Biophysica Acta
Swathi Banthiya, Jacqueline Kalms, Etienne Galemou Yoga, Igor Ivanov, Xavi Carpena, Mats Hamberg, Hartmut Kuhn, Patrick Scheerer
Pseudomonas aeruginosa expresses a secreted LOX-isoform (PA-LOX, LoxA) capable of oxidizing polyenoic fatty acid to hydroperoxy derivatives. Here we report high-level expression of this enzyme in E. coli and its structural and functional characterization. Recombinant PA-LOX oxygenates polyenoic fatty acids including eicosapentaenoic acid and docosahexaenoic acid to the corresponding (n-6)S-hydroperoxy derivatives. This reaction involves abstraction of the proS-hydrogen from the n-8 bisallylic methylene. PA-LOX lacks major leukotriene synthase activity but converts 5S-HETE and 5S,6R/S-DiHETE to anti-inflammatory and pro-resolving lipoxins...
August 5, 2016: Biochimica et Biophysica Acta
Qiong Cheng, Zheng Wang, Ruihua Ma, Yongtao Chen, Yan Yan, Shuo Miao, Jingyu Jiao, Xue Cheng, Lingfei Kong, Duyun Ye
Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis...
October 2016: International Immunopharmacology
Felice Simiele, Antonio Recchiuti, Sara Patruno, Roberto Plebani, Anna Maria Pierdomenico, Marilina Codagnone, Mario Romano
Lipoxin (LX) A4, a main stop signal of inflammation, exerts potent bioactions by activating a specific G protein-coupled receptor, termed formyl peptide receptor 2 and recently renamed ALX/FPR2. Knowledge of the regulatory mechanisms that drive ALX/FPR2 gene expression is key for the development of innovative anti-inflammatory pharmacology. Here, we examined chromatin patterns of the ALX/FPR2 gene. We report that in MDA-MB231 breast cancer cells, the ALX/FPR2 gene undergoes epigenetic silencing characterized by low acetylation at lysine 27 and trimethylation at lysine 4, associated with high methylation at lysine 27 of histone 3...
October 2016: Biochimica et Biophysica Acta
Dan Yan, Hai-Ling Liu, Zhong-Jian Yu, Yong-Hong Huang, Dian Gao, Hua Hao, Shou-Sheng Liao, Fang-Yun Xu, Xiao-Yan Zhou
Lipoxins (LXs) display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S),6(R),7-trihydroxyheptanoic acid methyl ester), the agonist of lipoxin A₄ receptor, in a model of Lipopolysaccharides (LPS) and d-Galactosamine (d-GalN) induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO) were examined to evaluate the levels of neutrophil infiltration...
2016: International Journal of Molecular Sciences
Susan Adel, Felix Karst, Àngels González-Lafont, Mária Pekárová, Patricia Saura, Laura Masgrau, José M Lluch, Sabine Stehling, Thomas Horn, Hartmut Kuhn, Dagmar Heydeck
ALOX15 (12/15-lipoxygenase) orthologs have been implicated in maturational degradation of intracellular organelles and in the biosynthesis of antiinflammatory and proresolving eicosanoids. Here we hypothesized that lower mammals (mice, rats, pigs) express 12-lipoxygenating ALOX15 orthologs. In contrast, 15-lipoxygenating isoforms are found in higher primates (orangutans, men), and these results suggest an evolution of ALOX15 specificity. To test this hypothesis we first cloned and characterized ALOX15 orthologs of selected Catarrhini representing different stages of late primate evolution and found that higher primates (men, chimpanzees) express 15-lipoxygenating orthologs...
July 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
A Trovato, R Siracusa, R Di Paola, M Scuto, M L Ontario, Ornella Bua, Paola Di Mauro, M A Toscano, C C T Petralia, L Maiolino, A Serra, S Cuzzocrea, Vittorio Calabrese
BACKGROUND: There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. RESULTS: Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat...
2016: Immunity & Ageing: I & A
Xue Han, Weifeng Yao, Zipeng Liu, Haobo Li, Zhong-Jun Zhang, Ziqing Hei, Zhengyuan Xia
Oxidative stress plays a critical role in the pathogenesis of intestinal ischemia reperfusion (IIR) injury. Enhancement in endogenous Lipoxin A4 (LXA4), a potent antioxidant and mediator, is associated with attenuation of IIR. However, the effects of LXA4 on IIR injury and the potential mechanisms are unknown. In a rat IIR (ischemia 45 minutes and subsequent reperfusion 6 hours) model, IIR caused intestinal injury, evidenced by increased serum diamine oxidase, D-lactic acid, intestinal-type fatty acid-binding protein, and the oxidative stress marker 15-F2t-Isoprostane...
2016: Oxidative Medicine and Cellular Longevity
Jesmond Dalli, Charles Serhan
Macrophages and neutrophils orchestrate acute inflammation and host defense as well as the resolution phase and return to homeostasis. In this article, we review the contribution of macrophages to local lipid mediator (LM) levels and the regulation of macrophage LM profiles by polymorphonuclear neutrophils and neutrophil-derived microparticles. We carried out LM metabololipidomics, profiling distinct phagocytes: neutrophils (PMNs), apoptotic PMNs, and macrophages. Efferocytosis increased specialized proresolving mediator (SPM) biosynthesis, including resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles...
June 2016: Microbiology Spectrum
Kosaku Murakami
  While arachidonic acid (AA), which is classified into n-6 polyunsaturated fatty acid (PUFA), has been mainly recognized as a substrate of pro-inflammatory mediators, eicosapentaenoic acid or docosahexaenoic acid, which are classified into n-3 PUFA, is currently identified as substrates of mediators inducing resolution of inflammation, namely pro-resolving mediators (SPM). As with any other pathological conditions, it is gradually elucidated that SPMs contributes a certain effect on joint inflammation. In osteoarthritis (OA), Lipid fractions extracted from adipocytes, especially in infrapatellar fat pad rather than subcutaneous tissue induce T cell skewing for producing IFN-γ or decrease the production of IL-12p40 from macrophages...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Christopher Beermann, Sandy Neumann, Daniela Fußbroich, Stefan Zielen, Ralf Schubert
Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil-associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil-derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies...
November 2016: Nutrition
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