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Allergology International : Official... Jan 2015Prostanoids, which include prostaglandin and thromboxane, are metabolites of arachidonic acid released in various pathophysiological conditions. They induce a range of... (Review)
Review
Prostanoids, which include prostaglandin and thromboxane, are metabolites of arachidonic acid released in various pathophysiological conditions. They induce a range of actions mediated through their respective receptors expressed on target cells. It has been demonstrated that each prostanoid receptor has multiple functions and that the effect of receptor stimulation can vary depending on context; this sometimes results in opposing effects, such as simultaneous excitatory and inhibitory outcomes. The balance between the production of each prostanoid and the expression of its receptors has been shown to be important for maintaining homeostasis but also involved in the development of various pathological conditions such as allergy. Here, we review the recent findings on the roles of prostanoids in allergy, especially focusing on atopic dermatitis and asthma.
Topics: Animals; Asthma; Dermatitis, Atopic; Humans; Hypersensitivity; Prostaglandins; Pruritus; Skin
PubMed: 25572554
DOI: 10.1016/j.alit.2014.08.002 -
Theranostics 2021: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability ( lung transplantation) or, do not effectively...
: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability ( lung transplantation) or, do not effectively prolong patient survival time ( lung lavage). There is thus an urgent clinical need for effective drugs to retard the progression of silicosis. : To systematically characterize the molecular changes associated with silicosis and to discover potential therapeutic targets, we conducted a transcriptomics analysis of human lung tissues acquired during transplantation, which was integrated with transcriptomics and metabolomics analyses of silicosis mouse lungs. The results from the multi-omics analyses were then verified by qPCR, western blot, and immunohistochemistry. The effect of Ramatroban on the progression of silicosis was evaluated in a silica-induced mouse model. : Wide metabolic alterations were found in lungs from both human patients and mice with silicosis. Targeted metabolite quantification and validation of expression of their synthases revealed that arachidonic acid (AA) pathway metabolites, prostaglandin D (PGD) and thromboxane A (TXA), were significantly up-regulated in silicosis lungs. We further examined the effect of Ramatroban, a clinical antagonist of both PGD and TXA receptors, on treating silicosis using a mouse model. The results showed that Ramatroban significantly alleviated silica-induced pulmonary inflammation, fibrosis, and cardiopulmonary dysfunction compared with the control group. : Our results revealed the importance of AA metabolic reprogramming, especially PGD and TXA in the progression of silicosis. By blocking the receptors of these two prostanoids, Ramatroban may be a novel potential therapeutic drug to inhibit the progression of silicosis.
Topics: Animals; Biomarkers; Case-Control Studies; Female; Humans; Lung; Male; Metabolome; Mice; Prostaglandin D2; Silicosis; Thromboxane A2; Transcriptome
PubMed: 33500731
DOI: 10.7150/thno.47627 -
Journal of the American College of... Jul 2022
Topics: Aspirin; Blood Platelets; Humans; Thromboxane B2; Thromboxanes
PubMed: 35835497
DOI: 10.1016/j.jacc.2022.04.053 -
Marine Drugs Jul 2019Prostaglandins (PGs) are lipid mediators belonging to the eicosanoid family. PGs were first discovered in mammals where they are key players in a great variety of... (Review)
Review
Prostaglandins (PGs) are lipid mediators belonging to the eicosanoid family. PGs were first discovered in mammals where they are key players in a great variety of physiological and pathological processes, for instance muscle and blood vessel tone regulation, inflammation, signaling, hemostasis, reproduction, and sleep-wake regulation. These molecules have successively been discovered in lower organisms, including marine invertebrates in which they play similar roles to those in mammals, being involved in the control of oogenesis and spermatogenesis, ion transport, and defense. Prostaglandins have also been found in some marine macroalgae of the genera and and very recently the PGs pathway has been identified for the first time in some species of marine microalgae. In this review we report on the occurrence of prostaglandins in the marine environment and discuss the anti-inflammatory role of these molecules.
Topics: Animals; Anthozoa; Anti-Inflammatory Agents; Aquatic Organisms; Gracilaria; Laminaria; Microalgae; Prostaglandins; Thromboxanes
PubMed: 31340503
DOI: 10.3390/md17070428 -
International Journal of Molecular... Oct 2021Cardiovascular diseases are currently among the leading causes of morbidity and mortality in many developed countries. They are distinguished by chronic and latent... (Review)
Review
Cardiovascular diseases are currently among the leading causes of morbidity and mortality in many developed countries. They are distinguished by chronic and latent development, a course with stages of worsening of symptoms and a period of improvement, and a constant potential threat to life. One of the most important disorders in cardiovascular disease is ischemic stroke. The causes of ischemic stroke can be divided into non-modifiable and modifiable causes. One treatment modality from a neurological point of view is acetylsalicylic acid (ASA), which blocks cyclooxygenase and, thus, thromboxane synthesis. The legitimacy of its administration does not raise any doubts in the case of the acute phase of stroke in patients in whom thrombolytic treatment cannot be initiated. The measurement of thromboxane B2 (TxB2) in serum (a stable metabolic product of TxA2) is the only test that measures the effect of aspirin on the activity of COX-1 in platelets. Measurement of thromboxane B2 may be a potential biomarker of vascular disease risk in patients treated with aspirin. The aim of this study is to present the role of thromboxane B2 in ischemic stroke and to present effective therapies for the treatment of ischemic stroke. Scientific articles from the PubMed database were used for the work, which were selected on the basis of a search for "thromboxane and stroke". Subsequently, a restriction was introduced for works older than 10 years, those concerning animals, and those without full text access. Ultimately, 58 articles were selected. It was shown that a high concentration of TXB2 may be a risk factor for ischemic stroke or ischemic heart disease. However, there is insufficient evidence to suggest that thromboxane could be used in clinical practice as a marker of ischemic stroke. The inclusion of ASA in the prevention of stroke has a beneficial effect that is associated with the effect on thromboxane. However, its insufficient power in 25% or even 50% of the population should be taken into account. An alternative and/or additional therapy could be a selective antagonist of the thromboxane receptor. Thromboxane A2 production is inhibited by estrogen; therefore, the risk of CVD after the menopause and among men is higher. More research is needed in this area.
Topics: Animals; Aspirin; Cardiovascular Diseases; Fibrinolytic Agents; Humans; Ischemic Stroke; Thromboxane B2
PubMed: 34769074
DOI: 10.3390/ijms222111644 -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
Frontiers in Pharmacology 2022Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids in cells. PUFAs regulate cellular function through the formation of derived lipid... (Review)
Review
Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids in cells. PUFAs regulate cellular function through the formation of derived lipid mediators termed eicosanoids. The oxygenation of 20-carbon PUFAs via the oxygenases cyclooxygenases, lipoxygenases, or cytochrome P450, generates a class of classical eicosanoids including prostaglandins, thromboxanes and leukotrienes, and also the more recently identified hydroxy-, hydroperoxy-, epoxy- and oxo-eicosanoids, and the specialized pro-resolving (lipid) mediators. These eicosanoids play a critical role in the regulation of inflammation in the blood and the vessel. While arachidonic acid-derived eicosanoids are extensively studied due to their pro-inflammatory effects and therefore involvement in the pathogenesis of inflammatory diseases such as atherosclerosis, diabetes mellitus, hypertension, and the coronavirus disease 2019; in recent years, several eicosanoids have been reported to attenuate exacerbated inflammatory responses and participate in the resolution of inflammation. This review focused on elucidating the biosynthesis and the mechanistic signaling of eicosanoids in inflammation, as well as the pro-inflammatory and anti-inflammatory effects of these eicosanoids in the blood and the vascular wall.
PubMed: 36238558
DOI: 10.3389/fphar.2022.997403 -
American Journal of Respiratory and... Sep 2022Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have...
Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We used TBXA2R-deficient mice and small-molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. TBXA2R expression was upregulated in fibroblasts in the lungs of patients with IPF and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting that an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes, which are nonenzymatic products of arachidonic acid induced by reactive oxygen species, were persistently elevated during fibrosis. F2-isoprostanes induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-β (transforming growth factor-β) signaling. treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.
Topics: Animals; Bleomycin; F2-Isoprostanes; Fibroblasts; Humans; Idiopathic Pulmonary Fibrosis; Lung; Mice; Mice, Inbred C57BL; Prostaglandins; Receptors, Thromboxane; Thromboxanes; Transforming Growth Factor beta
PubMed: 35728047
DOI: 10.1164/rccm.202106-1503OC -
Biomedicine & Pharmacotherapy =... Jul 2023Thromboxane (TX) and prostaglandins are metabolites of arachidonic acid, a twenty-carbon unsaturated fatty acid, and have a variety of actions that are exerted via... (Review)
Review
Thromboxane (TX) and prostaglandins are metabolites of arachidonic acid, a twenty-carbon unsaturated fatty acid, and have a variety of actions that are exerted via specific receptors. Angiogenesis is defined as the formation of new blood vessels from pre-existing vascular beds and is a critical component of pathological conditions, including inflammation and cancer. Lymphatic vessels play crucial roles in the regulation of interstitial fluid, immune surveillance, and the absorption of dietary fat from the intestine; and they are also involved in the pathogenesis of various diseases. Similar to angiogenesis, lymphangiogenesis, the formation of new lymphatic vessels, is a critical component of pathological conditions. The TP-dependent accumulation of platelets in microvessels has been reported to enhance angiogenesis under pathological conditions. Although the roles of some growth factors and cytokines in angiogenesis and lymphangiogenesis have been well characterized, accumulating evidence suggests that TX induces the production of proangiogenic and prolymphangiogenic factors through the activation of adenylate cyclase, and upregulates angiogenesis and lymphangiogenesis under disease conditions. In this review, we discuss the role of TX as a regulator of angiogenesis and lymphangiogenesis, and its emerging importance as a therapeutic target.
Topics: Humans; Lymphangiogenesis; Thromboxanes; Lymphatic Vessels; Neoplasms; Inflammation
PubMed: 37150029
DOI: 10.1016/j.biopha.2023.114831 -
Nutrients Jul 2021Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to... (Randomized Controlled Trial)
Randomized Controlled Trial
Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.
Topics: Adult; Anticholesteremic Agents; Berberine; Blood Pressure; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Heart Disease Risk Factors; Humans; Hyperlipidemias; Male; Middle Aged; Testosterone; Thromboxane A2; Triglycerides; Waist-Hip Ratio
PubMed: 34444711
DOI: 10.3390/nu13082550