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Giancarlo Marone, Maria Rosaria Galdiero, Antonio Pecoraro, Valentina Pucino, Gjada Criscuolo, Maria Triassi, Gilda Varricchi
Prostaglandin D2 (PGD2 ) is a major cyclooxygenase mediator that is synthesized by activated human mast cells and other immune cells. The biological effects of PGD2 are mediated by D-prostanoid (DP1 ), DP2 (CRTH2) and thromboxane prostanoid (TP) receptors that are expressed on several immune and non-immune cells involved in allergic inflammation. PGD2 exerts various proinflammatory effects relevant to the pathophysiology of allergic disorders. Several selective, orally active, DP2 receptor antagonists and a small number of DP1 receptor antagonists are being developed for the treatment of allergic disorders...
January 2019: Expert Opinion on Investigational Drugs
Daniel Elieh Ali Komi, Leif Bjermer
Improving the lung function after experimental allergen challenge by blocking of mast cell (MC) mediators and the capability of MC mediators (including histamine, prostaglandin (PG) D2, and leukotriene (LT) C4) in induction of mucosal edema, bronchoconstriction, and mucus secretion provide evidence that MCs play a key role in pathophysiology of asthma. In asthma, the number of MCs increases in the airways and infiltration of MCs in a variety of anatomical sites including the epithelium, the submucosal glands, and the smooth muscle bundles occurs...
November 30, 2018: Clinical Reviews in Allergy & Immunology
Tanya M Laidlaw
It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter's disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually involves nasal congestion, rhinorrhea, wheezing and bronchospasm. Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive...
September 2018: World Journal of Otorhinolaryngology—Head and Neck Surgery
Zhang L Zhang, Vincent van Suylen, Judith E van Zanden, Caroline Van De Wauwer, Erik A M Verschuuren, Wim van der Bij, Michiel E Erasmus
OBJECTIVES: Despite progress in lung transplantation (LTx) techniques, a shortage of donor lungs persists worldwide. Ex vivo lung perfusion (EVLP) is a technique that evaluates, optimizes and enables transplantation of the lungs that would otherwise have been discarded. Herein, we present our centre's first EVLP experiences between July 2012 and June 2016, when we performed 149 LTxs. METHODS: It was a single-centre, retrospective analysis of a prospectively collected database...
November 29, 2018: European Journal of Cardio-thoracic Surgery
Asheebo Rojas, Di Chen, Thota Ganesh, Nicholas H Varvel, Raymond Dingledine
Introduction:A robust neuroinflammatory response is a prevalent feature of multiple neurological disorders, including epilepsy and acute status epilepticus. One component of this neuroinflammatory reaction is the induction of cyclooxygenase-2 (COX-2), synthesis of several prostaglandins and endocannabinoid metabolites, and subsequent activation of prostaglandin and related receptors. Neuroinflammation mediated by COX-2 and its downstream effectors has received considerable attention as a potential target class to ameliorate the deleterious consequences of neurological injury...
November 28, 2018: Expert Opinion on Therapeutic Targets
Eri Takeshita, Hirofumi Komaki, Yuko Shimizu-Motohashi, Akihiko Ishiyama, Masayuki Sasaki, Shin'ichi Takeda
Objective: Currently, the only approved standard Duchenne muscular dystrophy (DMD) treatment in Japan is oral steroids, which have various disadvantages. Previous work has suggested that hematopoietic-type prostaglandin D synthase (HPGDS), involved in production of the inflammatory mediator prostaglandin D2 (PGD2 ), might have a role in DMD pathology. We therefore investigated the safety, pharmacokinetics (PK), and pharmacodynamics of a highly selective HPGDS inhibitor (TAS-205) in Japanese patients with genetically confirmed DMD...
November 2018: Annals of Clinical and Translational Neurology
Musaddique Hussain, Chengyun Xu, Minli Yao, Qin Zhang, Junsong Wu, Xiling Wu, Meiping Lu, Lanfang Tang, Fugen Wu, Ximei Wu
AIMS: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by overwhelming lung inflammation, are associated with high mortality. Cigarette smoke (CS) is one of the major causes of ALI/ARDS. Since high expression of prostaglandin (PG) D2 has been observed in CS-induced lung injury. Currently, no effective pharmacological therapies are available to treat ALI, and supportive therapies remain the mainstay of treatment. Therefore, we investigated the protective effect of CT‑133, a newly discovered selective CRTH2 antagonist, on CS-induced ALI in vivo and in vitro...
November 20, 2018: Life Sciences
Geum Jin Kim, Xian Li, Seong-Hwan Kim, Inho Yang, Dongyup Hahn, Jungwook Chin, Sang-Jip Nam, Joo-Won Nam, Doo Hyun Nam, Dong-Chan Oh, Hyeun Wook Chang, Hyukjae Choi
Six seongsanamides were isolated from the culture broth of Bacillus safensis KCTC 12796BP, and their structures were elucidated by spectroscopic data analysis combined with Marfey's method, electronic circular dichroism calculations, and biosynthetic gene cluster analysis. Compounds 1-4 were bicyclic peptides with isodityrosine residues; 5 and 6 were monocyclic peptides. Only the bicyclic seongsanamides inhibited degranulation and LTC4 /PGD2 generation in IgE/Ag-stimulated bone marrow-derived mast cells. Oral administration of 1 suppressed mast cell-dependent passive cutaneous anaphylaxis reaction...
November 20, 2018: Organic Letters
Atasi De Chatterjee, Debarshi Roy, Priscilla Guevara, Rituraj Pal, Mahesh Naryan, Sukla Roychowdhury, Siddhartha Das
Background: The migration of tumor cells is critical in spreading cancers through the lymphatic nodes and circulatory systems. Although arachidonic acid (AA) and its soluble metabolites have been shown to induce the migration of breast and colon cancer cells, the mechanism by which it induces such migration has not been fully understood. Objective: The effect of AA on migratory responses of the MDA-MB-231 cell line (a triple-negative breast cancer cell) was examined and compared with MCF-7 (estrogen-receptor positive) breast cancer cells to elucidate the mechanism of AA-induced migration...
2018: Clinical Cancer Drugs
Austin E F Sheppe, Evangel Kummari, Alyssa Walker, Angela Richards, Winnie W Hui, Jung Hwa Lee, Lauren Mangum, Abdolsamad Borazjani, Matthew K Ross, Mariola J Edelmann
Eicosanoids are cellular metabolites, which shape the immune response, including inflammatory processes in macrophages. The effects of these lipid mediators on inflammation and bacterial pathogenesis are not clearly understood. Certain eicosanoids are suspected to act as molecular sensors for the recruitment of neutrophils, while others regulate bacterial uptake. In this study, gene expression analyses indicated that genes involved in eicosanoid biosynthesis including COX-1, COX-2, DAGL, and PLA-2 are differentially regulated in THP-1 human macrophages infected with Salmonella enterica Typhimurium or Yersinia enterocolitica ...
2018: Frontiers in Microbiology
Brunda Tumala, Kathleen R Phelps, Stephanie Zhang, Somashubhra Bhattacharya, Laurie P Shornick
During respiratory viral infection, conventional dendritic cells (cDCs) take up antigen and migrate to the draining lymph nodes to present viral antigen and activate cytotoxic T lymphocytes; however, regulation of cDC activation and migration may be age dependent. In this study, we used a mouse model of paramyxoviral infection (Sendai virus) and demonstrated that cDCs, which have migrated from lungs to the draining lymph nodes, are delayed in expressing activation markers in neonatal mice compared with adults...
November 7, 2018: Viral Immunology
Aravind T Reddy, Sowmya P Lakshmi, Asoka Banno, Raju C Reddy
PPARδ belongs to the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors. Upon activation by an agonist, PPARδ controls a variety of physiological processes via regulation of its target genes. 15-deoxy-Δ12,14 -PGJ2 (15d-PGJ2 ) is a cyclopentenone prostaglandin that features an electrophilic, α, β-unsaturated ketone (an enone) in the cyclopentenone ring. Many of 15d-PGJ2 's biological effects result from covalent interaction between C9 and the thiol group of a catalytic cysteine (Cys) in target proteins...
November 6, 2018: ACS Chemical Biology
Chen-Di Lu, Ji-Kang Ma, Zheng-Yang Luo, Qun-Xi Tai, Pu Wang, Pei-Pei Guan
Transferrin (Tf) is an important iron-binding protein postulated to play a key role in iron ion (Fe) absorption via the Tf receptor (TfR), which potentially contributes to the pathogenesis of Alzheimer's disease (AD). However, the role of Tf in AD remains unknown. Using mouse-derived neurons and APP/PS1 transgenic (Tg) mice as model systems, we firstly revealed the mechanisms of APH-1α/1β and presenilin 1 (PS1) upregulation by Fe in prostaglandin (PG) E2 - and PGD2 -dependent mechanisms. Specifically, Fe stimulated the expression of mPGES-1 and the production of PGE2 and PGD2 via the Tf and TfR system...
November 1, 2018: Aging
Li-Na Qiao, Qiao-Ling Gao, Lian-Hong Tan, Yi-Nan Shi, Yan-Shu Jiang, Jiao-Jiao Yang, Yong-Sheng Yang
OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of single and multiple acupoints on sleep and concentrations of interlukin-1 β(IL-1 β), brain-derived neurotrophic factor (BDNF), prostaglandin D2 (PGD2 ) and melatonin (MLT, sleep-promoting factors) and corticosterone (CORT, awakening-promoting factor) in the serum in insomnia rats, so as to explore its efficacy difference and the mechanism underlying improving sleep. METHODS: Fifty-four male SD rats were randomly divided into control, model, EA-Baihui (GV 20), EA-Shenmen (HT 7), EA-Sanyinjiao (SP 6) and EA-GV 20+HT 7+SP 6 groups ( n =9 rats in each group)...
October 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Yoan Cherasse, Kosuke Aritake, Yo Oishi, Mahesh K Kaushik, Mustafa Korkutata, Yoshihiro Urade
Injection of nanomolar amounts of prostaglandin D2 (PGD2 ) into the rat brain has dose and time-dependent somnogenic effects, and the PGD2 -induced sleep is indistinguishable from physiologic sleep. Sleep-inducing PGD2 is produced in the brain by lipocalin-type PGD2 synthase (LPGDS). Three potential intracranial sources of LPGDS have been identified: oligodendrocytes, choroid plexus, and leptomeninges. We aimed at the identification of the site of synthesis of somnogenic PGD2 and therefore, generated a transgenic mouse line with the LPGDS gene amenable to conditional deletion using Cre recombinase (flox-LPGDS mouse)...
2018: Frontiers in Cellular Neuroscience
Wen-Liang Song, Emanuela Ricciotti, Xue Liang, Tilo Grosser, Gregory R Grant, Garret A FitzGerald
Prostaglandin (PG) D2 is formed by two distinct PGD synthases (PGDS): lipocalin-type PGDS (L-PGDS), which acts as a PGD2 -producing enzyme and as extracellular lipophilic transporter, and hematopoietic PGDS (H-PGDS), a σ glutathione-S-transferase. PGD2 plays an important role in the maintenance of vascular function; however, the relative contribution of L-PGDS- and H-PGDS-dependent formation of PGD2 in this setting is unknown. To gain insight into the function played by these distinct PGDS, we assessed systemic blood pressure (BP) and thrombogenesis in L-Pgds and H-Pgds knockout (KO) mice...
December 2018: Journal of Pharmacology and Experimental Therapeutics
Natália R T Amorim, Tatiana Luna-Gomes, Marcos Gama-Almeida, Glaucia Souza-Almeida, Claudio Canetti, Bruno L Diaz, Peter F Weller, Patricia Torres Bozza, Clarissa M Maya-Monteiro, Christianne Bandeira-Melo
Leptin is a cytokine, produced mainly by mature adipocytes, that regulates the central nervous system, mainly to suppress appetite and stimulate energy expenditure. Leptin also regulates the immune response by controlling activation of immunomodulatory cells, including eosinophils. While emerging as immune regulatory cells with roles in adipose tissue homeostasis, eosinophils have a well-established ability to synthesize pro-inflammatory molecules such as lipid mediators, a key event in several inflammatory pathologies...
2018: Frontiers in Immunology
Hiroki Kabata, Kazuyo Moro, Shigeo Koyasu
Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up-to-date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-κB pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+ -NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+ -NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1)...
November 2018: Immunological Reviews
Christian Domingo, Oscar Palomares, David A Sandham, Veit J Erpenbeck, Pablo Altman
Asthma is characterised by chronic airway inflammation, airway obstruction and hyper-responsiveness. The inflammatory cascade in asthma comprises a complex interplay of genetic factors, the airway epithelium, and dysregulation of the immune response.Prostaglandin D2 (PGD2 ) is a lipid mediator, predominantly released from mast cells, but also by other immune cells such as TH 2 cells and dendritic cells, which plays a significant role in the pathophysiology of asthma. PGD2 mainly exerts its biological functions via two G-protein-coupled receptors, the PGD2 receptor 1 (DP1 ) and 2 (DP2 )...
September 29, 2018: Respiratory Research
Irina Bobolea, Victoria Del Pozo, Veronica Sanz, Rosario Cabañas, Ana Fiandor, Carolina Alfonso-Carrillo, María Ángeles Salcedo, Rocío Heredia Revuelto, Santiago Quirce
BACKGROUND: Aspirin desensitization (AD) has been the only available modifying treatment in aspirin-exacerbated respiratory disease (AERD). The mechanisms of AD are nonetheless poorly understood. Though very effective, AD is limited by its risks and side-effects. OBJECTIVE: Moving forward to the targeted biologicals era, the aim of this study was to characterize the airway inflammatory response to long-term AD, including TSLP dynamics, in order to assess potential new targets in AERD...
October 2018: Respiratory Medicine
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