Prostaglandin D<sub>2</sub>receptor antagonists in allergic disorders: safety, efficacy, and future perspectives

Marone, Giancarlo; Galdiero, Maria Rosaria; Pecoraro, Antonio; Pucino, Valentina; Criscuolo, Gjada; Triassi, Maria; Varricchi, Gilda

doi:10.1080/13543784.2019.1555237

Cited by 55 publications

(49 citation statements)

References 151 publications

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“…Activated human mast cells can rapidly synthesize several lipid mediators [ 23 , 89 ]. Prostaglandin D 2 (PGD 2 ) is the main cyclooxygenase metabolite synthesized de novo by human mast cells [ 78 , 96 ]. Activated human mast cells also synthesize cysteinyl leukotriene C 4 (LTC 4 ) through the 5-lipoxygenase pathway [ 96 , 97 , 98 ].…”

Section: Resultsmentioning

confidence: 99%

“…Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary hypertension, and asthma, are currently a leading concern for patients with HIV infection [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. There is compelling evidence that mast cells and their proinflammatory and angiogenic mediators are involved in these disorders [ 26 , 32 , 33 , 45 , 78 ]. In this study we evaluated whether viral gp120 superantigen can induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from primary mast cells isolated from human lung parenchyma.…”

Section: Introductionmentioning

confidence: 99%

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HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

et al. 2020

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Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (VH3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE VH3+ bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

et al. 2020

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“…To date, numerous clinical trials have shown that DP2 antagonists are effective for patients with asthma ( Figure 1) [153][154][155]. Fevipiprant (QAW039), an oral DP2 antagonist, improved pulmonary function in asthmatic patients with severely impaired lung functions and patients with uncontrolled asthma using an inhaled corticosteroid (ICS) [132,133,156].…”

Section: Asthmamentioning

confidence: 99%

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Lee

Kim

2020

IJMS

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Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD 2 , PGI 2 , PGE 2 , PGF 2 , and thromboxane B 2 . PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.

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“…The effects of these drugs on the DP 2 receptor pathway may not be limited to asthma. DP 2 receptor expression is seen in mast cells and fibroblasts in nasal polyp tissue, on T cells in the nasal mucosa of patients with allergic rhinitis and in Th2 cells in patients with atopic dermatitis, indicating that there may also be potential for positive effects of DP 2 receptor antagonism in other organs and conditions . Data also suggest a potential role for antagonism of the DP 2 receptor pathway in reducing eosinophilic inflammation in patients with COPD, but not on clinical outcomes to date .…”

Section: Effects Of Dp2 Receptor Blockage On Asthmamentioning

confidence: 98%

The impact of the prostaglandin D₂ receptor 2 and its downstream effects on the pathophysiology of asthma

Brightling

Brusselle

Altman

2019

Allergy

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Current research suggests that the prostaglandin D2 (PGD2) receptor 2 (DP2) is a principal regulator in the pathophysiology of asthma, because it stimulates and amplifies the inflammatory response in this condition. The DP2 receptor can be activated by both allergic and nonallergic stimuli, leading to several pro‐inflammatory events, including eosinophil activation and migration, release of the type 2 cytokines interleukin (IL)‐4, IL‐5 and IL‐13 from T helper 2 (Th2) cells and innate lymphoid cells type 2 (ILCs), and increased airway smooth muscle mass via recruitment of mesenchymal progenitors to the airway smooth muscle bundle. Activation of the DP2 receptor pathway has potential downstream effects on asthma pathophysiology, including on airway epithelial cells, mucus hypersecretion, and airway remodelling, and consequently might impact asthma symptoms and exacerbations. Given the broad distribution of DP2 receptors on immune and structural cells involved in asthma, this receptor is being explored as a novel therapeutic target.

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Prostaglandin D₂receptor antagonists in allergic disorders: safety, efficacy, and future perspectives

Cited by 55 publications

References 151 publications

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

The impact of the prostaglandin D₂ receptor 2 and its downstream effects on the pathophysiology of asthma

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Prostaglandin D2receptor antagonists in allergic disorders: safety, efficacy, and future perspectives

Cited by 55 publications

References 151 publications

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

The impact of the prostaglandin D2 receptor 2 and its downstream effects on the pathophysiology of asthma

Contact Info

Product

Resources

About

Prostaglandin D₂receptor antagonists in allergic disorders: safety, efficacy, and future perspectives

The impact of the prostaglandin D₂ receptor 2 and its downstream effects on the pathophysiology of asthma