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Youn Yi Jo, Ji Yeon Lee, Chul-Kyu Park
The neuropeptide substance P (SP) is expressed in primary sensory neurons and is commonly regarded as a "pain" neurotransmitter. Upon peripheral inflammation, SP activates the neurokinin-1 (NK-1) receptor and potentiates activity of transient receptor potential vanilloid subtype 1 (TRPV1), which is coexpressed by nociceptive neurons. Therefore, SP functions as an important neurotransmitter involved in the hypersensitization of inflammatory pain. Resolvin E1 (RvE1), derived from omega-3 polyunsaturated fatty acids, inhibits TRPV1 activity via activation of the chemerin 23 receptor (ChemR23)-an RvE1 receptor located in dorsal root ganglion neurons-and therefore exerts an inhibitory effect on inflammatory pain...
2016: Mediators of Inflammation
Jan M Keppel Hesselink, Flavia Chiosi, Ciro Costagliola
Resolvins are a novel class of lipid-derived endogenous molecules (autacoids) with potent immunomodulating properties, which regulate the resolution phase of an active immune response. These modulating factors are locally produced, influencing the function of cells and/or tissues, which are produced on demand and subsequently metabolized in the same cells and/or tissues. This review is focused on certain lipid autacoids with putative relevance for ophthalmology in general and for dry eye more specifically. We also briefly investigate the concept of aliamides and the role of palmitoylethanolamide in ophthalmology, and analyze in more detail the putative role and the preclinical and clinical development of resolvins as emerging treatments for dry eye and related disorders, with a focus on one of the lead resolvin derivatives - RX-10045...
2016: Drug Design, Development and Therapy
Karoline G Primdahl, Marius Aursnes, Mary E Walker, Romain A Colas, Charles N Serhan, Jesmond Dalli, Trond V Hansen, Anders Vik
Specialized pro-resolving lipid mediators are biosynthesized during the resolution phase of acute inflammation from n-3 polyunsaturated fatty acids. Recently, the isolation and identification of the four novel mediators denoted 13-series resolvins, namely, RvT1 (1), RvT2 (2), RvT3 (3) and RvT4 (4), were reported, which showed potent bioactions characteristic for specialized pro-resolving lipid mediators. Herein, based on results from LC/MS-MS metabololipidomics and the stereoselective synthesis of 13(R)-hydroxy-7Z,10Z,13R,14E,16Z,19Z docosapentaenoic acid (13R-HDPA, 5), we provide direct evidence that the four novel mediators 1-4 are all biosynthesized from the pivotal intermediate 5...
October 5, 2016: Journal of Natural Products
Justin T Easley, Christina L M Maruyama, Ching-Shuen Wang, Olga J Baker
Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic inflammation and destruction of salivary and lacrimal glands leading to dry mouth and dry eyes, respectively. Currently, the etiology of SS is unknown and the current therapies have no permanent benefit; therefore, new approaches are necessary to effectively treat this condition. Resolvins are highly potent endogenous lipid mediators that are synthesized during the resolution of inflammation to restore tissue homeostasis. Previous studies indicate that the resolvin family member, RvD1, binds to the ALX/FPR2 receptor to block inflammatory signals caused by tumor necrosis factor-alpha (TNF-α) in the salivary epithelium...
October 2016: Physiological Reports
Sam Famenini, Elizabeth A Rigali, Henry M Olivera-Perez, Johnny Dang, Michael To Chang, Ramesh Halder, Rammohan V Rao, Matteo Pellegrini, Verna Porter, Dale Bredesen, Milan Fiala
Monocyte/macrophages of patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are defective in phagocytosis and degradation amyloid-β 1-42 (Aβ1-42), but are improved by ω-3 fatty acids (ω-3). The hypothesis of this study was that active Aβ1-42 phagocytosis by macrophages prevents brain amyloidosis and thus maintains cognition. We studied the effects of self-supplementation with a drink with ω-3, antioxidants, and resveratrol on Mini-Mental State Examination (MMSE) scores, macrophage M1M2 phenotype (the ratio of inflammatory CD54+CD80 and proresolution markers CD163+CD206), and Aβ1-42 phagocytosis in patients initially diagnosed as having MCI or subjective cognitive impairment (SCI)...
September 27, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Gabrielle Fredman, Jason Hellmann, Jonathan D Proto, George Kuriakose, Romain A Colas, Bernhard Dorweiler, E Sander Connolly, Robert Solomon, David M Jones, Eric J Heyer, Matthew Spite, Ira Tabas
Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions...
September 23, 2016: Nature Communications
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
Jesmond Dalli, Romain A Colas, Carolina Quintana, Diana Barragan-Bradford, Shelley Hurwitz, Bruce D Levy, Augustine M Choi, Charles N Serhan, Rebecca M Baron
OBJECTIVE: To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. DESIGN: Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. SETTING: Brigham and Women's Hospital Medical Intensive Care Unit...
September 14, 2016: Critical Care Medicine
Bangwei Luo, Fuyu Han, Kai Xu, Jinsong Wang, Zongwei Liu, Zigang Shen, Jia Li, Yu Liu, Man Jiang, Zhi-Yuan Zhang, Zhiren Zhang
UNLABELLED: Experimental autoimmune neuritis (EAN) is the animal model of human acute inflammatory demyelinating polyradiculoneuropathies (AIDP), an auto-immune inflammatory demyelination disease of the peripheral nervous system (PNS) and the world's leading cause of acute autoimmune neuromuscular paralysis. EAN and AIDP are characterized by self-limitation with spontaneous recovery; however, endogenous pathways that regulate inflammation resolution in EAN and AIDP remain elusive. A pathway of endogenous mediators, especially resolvins and clearance of apoptotic cells, may be involved...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nicolas H Pope, Morgan Salmon, John P Davis, Anuran Chatterjee, Gang Su, Michael S Conte, Gorav Ailawadi, Gilbert R Upchurch
The role of resolvins in abdominal aortic aneurysm (AAA) has not been established. We hypothesized that treatment with D-series resolvins (RvD2 or RvD1) would attenuate murine AAA formation through alterations in macrophage polarization and cytokine expression. Male C57/B6 mice (n = 9 per group) 8 to 12 wk old received RvD2 (100 ng/kg/treatment), RvD1 (100 ng/kg/treatment), or vehicle only every third day beginning 3 d before abdominal aortic perfusion with elastase as prevention. Aortas were collected 14 d after elastase perfusion...
September 12, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Pongsatorn Meesawatsom, James Burston, Gareth Hathway, Andrew Bennett, Victoria Chapman
BACKGROUND: Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects...
2016: Journal of Neuroinflammation
Xuan Yin, Xiong-Wei Yu, Pan Zhu, Yuan-Ming Zhang, Xiao-Hong Zhang, Feng Wang, Jin-Jie Zhang, Wang Yan, Yang Xi, Jian-Bo Wan, Jing-Xuan Kang, Zu-Quan Zou, Shi-Zhong Bu
Malignant melanoma is the most lethal form of skin cancer. Although preclinical studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are beneficial for prevention of melanoma, the molecular mechanisms underlying the protective effects of n‑3 PUFAs on melanoma remain largely unknown. In the present study, endogenously increased levels of n-3 PUFAs in the tumor tissues of omega‑3 fatty acid desaturase (fat‑1) transgenic mice was associated with a reduction in the growth rate of melanoma xenografts...
October 2016: Molecular Medicine Reports
Yu Liu, Xiaolong Yuan, Wenhui Li, Qianqian Cao, Yusheng Shu
Transforming growth factor-β1 (TGF-β1) is a potent stimulator of the epithelial-to-mesenchymal transition (EMT), which is a key event in the initiation of tumor cell metastasis. Aspirin-triggered resolvin D1 (AT-RvD1) is known to be involved in the resolution of inflammation; however, whether AT-RvD1 exerts effects on TGF-β1-induced EMT remains unclear. Thus, we first explored the effects of AT-RvD1 on the EMT of lung cancer cells. Treatment with TGF-β1 increased the level of reactive oxygen species (ROS) and reduced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)...
October 2016: International Journal of Molecular Medicine
Valerio Chiurchiù, Alessandro Leuti, Jesmond Dalli, Anders Jacobsson, Luca Battistini, Mauro Maccarrone, Charles N Serhan
Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate...
August 24, 2016: Science Translational Medicine
Maximilian Neumann, Elisabeth M Meier, Lisa Rein-Fischboeck, Sabrina Krautbauer, Kristina Eisinger, Charalampos Aslanidis, Rebekka Pohl, Thomas S Weiss, Christa Buechler
The chemokine-like receptor 1 (CMKLR1) ligands resolvin E1 and chemerin are known to modulate inflammatory response. The progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is associated with inflammation. Here it was analyzed whether hepatic CMKLR1 expression is related to histological features of NASH. Therefore, CMKLR1 mRNA was quantified in liver tissue of 33 patients without NAFLD, 47 patients with borderline NASH and 38 patients with NASH. Hepatic CMKLR1 mRNA was not associated with gender and body mass index (BMI) in the controls and the whole study group...
2016: International Journal of Molecular Sciences
Chun-Teh Lee, Ricardo Teles, Alpdogan Kantarci, Tsute Chen, Jon McCafferty, Jacqueline R Starr, Luciana Carla Neves Brito, Bruce J Paster, Thomas E Van Dyke
Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Hildur H Arnardottir, Jesmond Dalli, Lucy V Norling, Romain A Colas, Mauro Perretti, Charles N Serhan
Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rvs) are a new family from the endogenous specialized proresolving mediators (SPMs) that actively stimulate resolution of inflammation. In this study, using lipid mediator metabololipidomics with murine joints we found a temporal regulation of endogenous SPMs during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series Rvs, for example, RvD1, RvD2, RvD3, and RvD4...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Joana R Viola, Patricia Lemnitzer, Yvonne Jansen, Gergely Csaba, Carla Winter, Carlos Neideck, Carlos Silvestre-Roig, Gunnar Dittmar, Yvonne Döring, Maik Drechsler, Christian Weber, Ralf Zimmer, Nicolas Cenac, Oliver Soehnlein
RATIONALE: Atheroprogression is a consequence of nonresolved inflammation, and currently a comprehensive overview of the mechanisms preventing resolution is missing. However, in acute inflammation, resolution is known to be orchestrated by a switch from inflammatory to resolving lipid mediators. Therefore, we hypothesized that lesional lipid mediator imbalance favors atheroprogression. OBJECTIVE: To understand the lipid mediator balance during atheroprogression and to establish an interventional strategy based on the delivery of resolving lipid mediators...
October 14, 2016: Circulation Research
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
Konstantin Tsoyi, Sean R R Hall, Jesmond Dalli, Romain A Colas, Sailaja Ghanta, Bonna Ith, Anna Coronata, Laura E Fredenburgh, Rebecca M Baron, Augustine M K Choi, Charles N Serhan, Xiaoli Liu, Mark A Perrella
OBJECTIVES: Mesenchymal stromal cells are being investigated as a cell-based therapy for a number of disease processes, with promising results in animal models of systemic inflammation and sepsis. Studies are ongoing to determine ways to further improve the therapeutic potential of mesenchymal stromal cells. A gas molecule that improves outcome in experimental sepsis is carbon monoxide. We hypothesized that preconditioning of mesenchymal stromal cells with carbon monoxide ex vivo would promote further therapeutic benefit when cells are administered in vivo after the onset of polymicrobial sepsis in mice...
August 10, 2016: Critical Care Medicine
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