eicosanoids
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Eicosanoids are biologically active lipid mediators, comprising prostaglandins, leukotrienes, thromboxanes, and lipoxins, involved in several pathophysiological processes relevant to asthma, allergies, and allied diseases. Prostaglandins and leukotrienes are the most studied eicosanoids and established inducers of airway pathophysiology including bronchoconstriction and airway inflammation. Drugs inhibiting the synthesis of lipid mediators or their effects, such as leukotriene synthesis inhibitors, leukotriene receptors antagonists, and more recently prostaglandin D2 receptor antagonists, have been shown to modulate features of asthma and allergic diseases. This review, produced by an European Academy of Allergy and Clinical Immunology (EAACI) task force, highlights our current understanding of eicosanoid biology and its role in mediating human pathology, with a focus on new findings relevant for clinical practice, development of novel therapeutics, and future research opportunities.
- Klíčová slova
- asthma, food allergy, inflammation, leukotrienes, lipid mediators, prostaglandins, rhinitis,
- MeSH
- alergie * MeSH
- bronchiální astma * etiologie MeSH
- ikosanoidy MeSH
- konsensus MeSH
- leukotrieny MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- ikosanoidy MeSH
- leukotrieny MeSH
INTRODUCTION: The role of eicosanoids, metabolites of arachidonic acid with cardio-renal activity, remains unclear in human heart failure (HF). METHODS: We enrolled 50 patients with HF to measure plasma 14,15-EET and 14,15-DHET levels using commercial ELISA kits and compared them with 25 age- and sex-matched controls. RESULTS: Both of the measured eicosanoids were significantly higher in the HF group: 14,15-EET (91.3 ±25.7 ng/ml vs. 64.95 ±35.4 ng/ml) and 14,15-DHET (10.58 ±2.06 ng/ml vs. 9.07 ±1.60 ng/ml), p for both < 0.001. CONCLUSIONS: We found that peripheral plasma eicosanoid (14,15-EET, 14,15-DHET) levels are raised in patients with HF compared to age- and sex-matched controls.
- Klíčová slova
- dihydroxyeicosatrienoic acid, eicosanoids, epoxyeicosatrienoic acid, heart failure,
- Publikační typ
- časopisecké články MeSH
Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research.
- Klíčová slova
- COVID-19, LTRA, NSAID, asthma, biologicals,
- MeSH
- alergie * farmakoterapie MeSH
- antiflogistika nesteroidní farmakologie terapeutické užití MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- bronchiální astma * farmakoterapie MeSH
- farmakoterapie COVID-19 * MeSH
- ikosanoidy metabolismus MeSH
- konsensus MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- zánět farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- antivirové látky MeSH
- ikosanoidy MeSH
The interactions between drugs suppressing the production of arachidonic acid metabolites-eicosanoids and transforming growth factor beta 1 (TGF-beta 1) were investigated using CCL64 cells. These experiments, designed as complete factorial combination of treatments, demonstrated that both esculetin and eicosatetraynoic acid significantly potentiated the inhibitory effect of TGF-beta 1 on [3H]thymidine incorporation. The expression of overadditive effects depended both on the type and concentration of combined factors. These results corresponded with cell cycle analysis data (increased cell number in G1 and decreased cell number in S and G2/M phases) and with the results monitoring cell number following treatment with eicosatetraynoic acid, esculetin, 3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-di methyl propanoic acid (MK-886) and indomethacin. Summarizing, the degree of significance of combined effects supports the hypothesis of synergistic potentiation of TGF-beta 1 effects caused by eicosanoid inhibitors. The results indicate that either the lack of some eicosanoids or a certain type of misbalance in the metabolism of arachidonic acid leading to its abundance might modulate TGF-beta 1 effects on the cell cycle and proliferation in CCL64 cells.
- MeSH
- buněčné dělení účinky léků MeSH
- epitel účinky léků MeSH
- ikosanoidy farmakologie MeSH
- kyselina arachidonová metabolismus MeSH
- norek MeSH
- plíce účinky léků MeSH
- transformující růstový faktor beta farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ikosanoidy MeSH
- kyselina arachidonová MeSH
- transformující růstový faktor beta MeSH
Eicosanoids are twenty-carbon compounds derived from arachidonic acid. Lipoxygenases, cyclooxygenases and cytochrome P-450 enzymes contribute to their synthesis. Our review is focused on prostaglandins, leucotrienes, lipoxins, hepoxilins, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids. Most of these compounds have multiple functions and they also participate in blood pressure regulation and excretion of water and solutes in the kidney. They have some roles in the patogenesis of kidney disease, too. Both experimental models (mainly geneticaly modified mice and rats) and human epidemiological and genetical studies are used in the investigation of eicosanoid physiological and patophysiological functions. New information about their enzymatic regulations and receptors have already resulted in the development of new drugs, mainly antiasthmatics, but further investigation should bring about new results in the treatment of hypertension and other cardiovascular and renal diseases.
- MeSH
- hypertenze patofyziologie MeSH
- ikosanoidy fyziologie MeSH
- krevní tlak fyziologie MeSH
- kyseliny arachidonové fyziologie MeSH
- ledviny fyziologie patofyziologie MeSH
- lidé MeSH
- lipoxiny fyziologie MeSH
- lipoxygenasa fyziologie MeSH
- prostaglandiny fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ikosanoidy MeSH
- kyseliny arachidonové MeSH
- lipoxiny MeSH
- lipoxygenasa MeSH
- prostaglandiny MeSH
BACKGROUND: Eicosanoids act obviously as mediators of inflammation in ulcerative colitis. The objective of the submitted paper was to assess relations between intraluminal concentrations of prostaglandin E and leukotriene B4 and the activity of ulcerative colitis evaluated according to clinical, endoscopic and histological criteria. METHODS AND RESULTS: In 56 patients with ulcerative colitis the PGE concentration was assessed in the rectal dialysate (3H Prostaglandin E Radioimmunoassay Kit Ca-501, Clinical Assay Cambridge USA). In 35 patients with ulcerative colitis the authors assessed the LTB4 concentration in the rectal dialysate (Leukotriene B4 3H Assay RPN 70, Amersham, G. Britain). The authors proved a statistically significant correlation between the intraluminal PGE concentration and the activity of ulcerative colitis according to clinical criteria (p < 0.1), endoscopic criteria (p < 0.05) and histological criteria (p < 0.01). The intraluminal LTB4 concentration correlated significantly with the activity of ulcerative colitis according to clinical criteria (p < 0.05). When comparing LTB4 values with the activity of the disease according to endoscopic and histological criteria, a tendency of rising LTB4 values with increasing activity of the disease is apparent. However, a significant relationship was not found; this can be explained by the fact that relatively small groups of patients were investigated with a relatively great scatter of LTB4 concentrations. CONCLUSIONS: During the period of active ulcerative colitis the intraluminal PGE concentration rises and correlates with the clinical, endoscopic and histological activity. There is also a rise of the intraluminal LTB4 concentration which correlates with the clinical activity of the disease. A high eicosanoid concentration is found in cases with a severe course and complications.(ABSTRACT TRUNCATED AT 250 WORDS)
- MeSH
- dospělí MeSH
- leukotrien B4 biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- prostaglandiny E biosyntéza MeSH
- rektum metabolismus MeSH
- senioři MeSH
- ulcerózní kolitida metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- leukotrien B4 MeSH
- prostaglandiny E MeSH
- MeSH
- 6-ketoprostaglandin F1 alfa krev MeSH
- dospělí MeSH
- kyseliny ikosanové krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida krev MeSH
- thromboxan B2 krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- 6-ketoprostaglandin F1 alfa MeSH
- kyseliny ikosanové MeSH
- thromboxan B2 MeSH
Formosan subterranean termites (FST) were exposed to strains of Beauveria pseudobassiana (Bpb) and Isaria fumosorosea (Ifr) to determine virulence of the fungi. Once lethality was determined, sublethal doses of Bpb were combined with enzymes capable of degrading the insect cuticle to measure the potential to enhance fungal infection. Bpb applied to FST in combination with proteinases and a chitinase caused increased mortality over the fungus alone. Mortality was enhanced when Ifr was applied to FST in combination with a chitinase isolated from Serratia marcesans. A lipase isolated from Pseudomonas cepacia, when combined with Ifr, also resulted in greater mortality than all control treatments. FST were also exposed to the eicosanoid biosynthesis inhibitors (EBIs) dexamethasone (DEX), ibuprofen (IBU), and ibuprofen sodium salt (IBUNA), in combination with Ifr. Combining Ifr with IBUNA caused significantly increased mortality on days 6, 7, and 9. Cuticle-degrading enzymes and EBIs may have potential to enhance the pathogenic effect of a fungal control agent against the Formosan subterranean termite.
- MeSH
- analýza přežití MeSH
- chitinasy metabolismus MeSH
- dexamethason metabolismus MeSH
- dezinsekce metody MeSH
- Hypocreales růst a vývoj metabolismus MeSH
- ibuprofen metabolismus MeSH
- ikosanoidy antagonisté a inhibitory MeSH
- insekticidy metabolismus MeSH
- Isoptera metabolismus mikrobiologie fyziologie MeSH
- lipasa metabolismus MeSH
- proteasy metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chitinasy MeSH
- dexamethason MeSH
- ibuprofen MeSH
- ikosanoidy MeSH
- insekticidy MeSH
- lipasa MeSH
- proteasy MeSH
Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.
- Klíčová slova
- Colon cancer, Faeces, LC-MS, Metabolomics, nanoESI, nanoLC,
- MeSH
- chromatografie kapalinová * MeSH
- feces chemie MeSH
- fosfolipidy analýza MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací * MeSH
- ikosanoidy analýza MeSH
- lidé MeSH
- metabolom * MeSH
- metabolomika MeSH
- pilotní projekty MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- žlučové kyseliny a soli analýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfolipidy MeSH
- ikosanoidy MeSH
- žlučové kyseliny a soli MeSH
The leukotrienes and other lipoxygenase-derived metabolites of the arachidonic acid were proved to possess various biological activities and to participate in a number of pathological states and diseases, especially those associated with inflammatory processes and with altered immune response. The present paper reviews the role of these eicosanoids in the regulation of natural-killer cell activity and in production and action of some cytokines including interferons. Furthermore, the participation of the arachidonic acid lipoxygenase metabolism in the virus-host interaction and the relation of these findings to some experimental and human diseases is discussed.
- MeSH
- buňky NK imunologie MeSH
- fyziologie virů MeSH
- ikosanoidy biosyntéza fyziologie MeSH
- interferony biosyntéza fyziologie MeSH
- interleukiny biosyntéza metabolismus MeSH
- kyseliny arachidonové metabolismus MeSH
- leukotrieny biosyntéza fyziologie MeSH
- lidé MeSH
- roztroušená skleróza etiologie MeSH
- virové nemoci imunologie metabolismus mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ikosanoidy MeSH
- interferony MeSH
- interleukiny MeSH
- kyseliny arachidonové MeSH
- leukotrieny MeSH