9 – Lipid Mediators of Hypersensitivity and Inflammation

Published on Jan 1, 2014
· DOI :10.1016/B978-0-323-08593-9.00010-3
R. Stokes Peebles60
Estimated H-index: 60
Joshua A. Boyce67
Estimated H-index: 67
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1 Author (Nicolas G. Bazan)
1 Author (G. P. Lewis)
#1Elena A. Goncharova (UPenn: University of Pennsylvania)H-Index: 31
#2Dmitry A. GoncharovH-Index: 20
Last. Reynold A. PanettieriH-Index: 95
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Severe asthma manifests as airway remodeling and irreversible airway obstruction, in part because of the proliferation and migration of human airway smooth muscle (HASM) cells. We previously reported that cyclic adenosine monophosphate–mobilizing agents, including β2-adrenergic receptor (β2AR) agonists, which are mainstay of asthma therapy, and prostaglandin E2 (PGE2), inhibit the migration of HASM cells, although the mechanism for this migration remains unknown. Vasodilator-stimulated phosphopr...
Prostaglandin E2 (PGE2) is an abundant lipid inflammatory mediator with potent but incompletely understood anti-inflammatory actions in the lung. Deficient PGE2 generation in the lung predisposes to airway hyperresponsiveness and aspirin intolerance in asthmatic individuals. PGE2-deficient ptges−/− mice develop exaggerated pulmonary eosinophilia and pulmonary arteriolar smooth-muscle hyperplasia compared with PGE2-sufficient controls when challenged intranasally with a house dust mite extract. W...
#1Stacy L. Dorris (Vandy: Vanderbilt University)H-Index: 4
#2R. Stokes PeeblesH-Index: 60
Prostacyclin, or PGI2, is an end product derived from the sequential metabolism of arachidonic acid via cyclooxygenase and PGI synthase (PGIS). The receptor for PGI2, IP, can be found on a variety of cell types and signaling through this receptor exhibits broad physiological effects. Historically, PGI2 has been understood to play a role in cardiovascular health, specifically having powerful vasodilatory effects via relaxation of smooth muscle and inhibiting of platelet aggregation. For these rea...
Atopic dermatitis (AD) skin lesions exhibit epidermal and dermal thickening, eosinophil infiltration, and increased levels of the cysteinyl leukotriene (cys-LT) leukotriene C4 (LTC4). Epicutaneous sensitization with ovalbumin of WT mice but not ΔdblGATA mice, the latter of which lack eosinophils, caused skin thickening, collagen deposition, and increased mRNA expression of the cys-LT generating enzyme LTC4 synthase (LTC4S). Skin thickening and collagen deposition were significantly reduced in ov...
#1Pawel Kalinski (University of Pittsburgh)H-Index: 68
PGE2, an essential homeostatic factor, is also a key mediator of immunopathology in chronic infections and cancer. The impact of PGE2 reflects the balance between its cyclooxygenase 2-regulated synthesis and 15-hydroxyprostaglandin dehydrogenase-driven degradation and the pattern of expression of PGE2 receptors. PGE2 enhances its own production but suppresses acute inflammatory mediators, resulting in its predominance at late/chronic stages of immunity. PGE2 supports activation of dendritic cell...
Summary Background CRTH2 is a G-protein-coupled receptor that mediates the activation of Th2 lymphocytes, eosinophils and basophils in response to prostaglandin D2 and may be involved in the pathogenesis of airway inflammation and dysfunction in asthma. Objective To evaluate the effects of a potent and selective CRTH2 antagonist, OC000459, on the lung function, symptoms and eosinophilic airway inflammation in a double-blind, parallel group trial in steroid-free subjects with moderate persistent ...
#1Tatiana Luna-Gomes (UFRJ: Federal University of Rio de Janeiro)H-Index: 8
#2Kelly Grace Magalhães (FIOCRUZ: Oswaldo Cruz Foundation)H-Index: 20
Last. Christianne Bandeira-Melo (UFRJ: Federal University of Rio de Janeiro)H-Index: 28
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PGD2 is a key mediator of allergic inflammatory diseases that is mainly synthesized by mast cells, which constitutively express high levels of the terminal enzyme involved in PGD2 synthesis, the hematopoietic PGD synthase (H-PGDS). In this study, we investigated whether eosinophils are also able to synthesize, and therefore, supply biologically active PGD2. PGD2 synthesis was evaluated within human blood eosinophils, in vitro differentiated mouse eosinophils, and eosinophils infiltrating inflamm...
#1James Buckley (NIH: National Institutes of Health)H-Index: 7
#2Mark A. BirrellH-Index: 50
Last. Maria G. BelvisiH-Index: 83
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Background Asthma and chronic obstructive pulmonary disease are airway inflammatory diseases characterised by airflow obstruction. Currently approved bronchodilators such as long-acting β 2 adrenoceptor agonists are the mainstay treatments but often fail to relieve symptoms of chronic obstructive pulmonary disease and severe asthma and safety concerns have been raised over long-term use. The aim of the study was to identify the receptor involved in prostaglandin E 2 (PGE 2 )-induced relaxation i...
#1Anna-Karin Larsson (KI: Karolinska Institutet)H-Index: 4
#2Annika Hagfjärd (KI: Karolinska Institutet)H-Index: 1
Last. Mikael Adner (KI: Karolinska Institutet)H-Index: 40
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Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD(2) in the guinea pig lung parenchyma. PGD(2) and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was mo...
#1Madison G. Boswell (Vandy: Vanderbilt University)H-Index: 9
#2Weisong Zhou (Vandy: Vanderbilt University)H-Index: 23
Last. R. Stokes Peebles (Vandy: Vanderbilt University)H-Index: 60
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Prostaglandin (PG)I2 has important regulatory functions on the innate and adaptive immune systems. Recent experimental evidence reveals that PGI2 modulates the development and function of CD4+ T cells subsets, including Th1, Th2, and Th17 cell responses. In vitro and in vivo studies support that PGI2 generally has an inhibitory effect on Th1 and Th2 activation, differentiation, and cytokine production. In contrast, PGI2 seems to enhance Th17-favoring polarization conditions, resulting in Th17 cy...
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#1J. Justin Mulvey (NewYork–Presbyterian Hospital)H-Index: 11
#2Cynthia M. Magro (NewYork–Presbyterian Hospital)H-Index: 75
Last. Amy Chadburn (NewYork–Presbyterian Hospital)H-Index: 34
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Abstract The anaphylatoxins produced by an unbridled complement cascade in atypical hemolytic uremic syndrome (aHUS) can alter the leukocyte environment in tissues and peripheral blood, causing clinically significant eosinophilia. While the membrane attack complex and C5a anaphlatoxin can be suppressed with anti-C5 biologics, the production of C3a is still capable of driving a destructive hypereosinophilic syndrome in spite of anticomplement therapy. The side-effects of glucocorticoids in treati...
#1Masaya Takemura (Kyoto University)H-Index: 16
#2Akio Niimi (Kyoto University)H-Index: 55
Last. Michiaki Mishima (Kyoto University)H-Index: 72
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Abstract Background Inhalation studies suggested "protective" roles of exogenous prostaglandin E 2 , but the clinical relevance of endogenous prostanoids in asthma is poorly known. The objective of this study is to measure sputum levels of prostanoids in asthmatic patients to correlate with clinical indices. Methods Mild ( n = 41) or moderate-to-severe (19) asthmatics and 27 normal controls were examined for pulmonary function (FEV 1 and mid-forced expiratory flow), sputum cell differentials, an...
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