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The Roles and Regulation of Prostaglandins within the Uterus
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Murray D. Mitchell, Sharlene Adamson, Curtis Coulam, Roberto J. Romero, Sarah Lundin-Schiller, Michael S. Trautman
Interleukin 8 or neutrophil activating protein 1 is a 72 amino acid protein that is produced in response to inflammation by a number of cell types such as monocytes, fibroblasts, and endothelial cells. It has actions as a chemoattractant and activator of neutrophils. In recent studies we have found that interleukin 8 has no direct action on amnion prostaglandin E2 production. In other cell types interleukin 8 has been shown to enhance arachidonate 5-lipoxygenase activity, although not the release of cellular arachidonate.103 Thus interleukin 8 must be regarded as an addition to the cytokines that may play a significant part in the mechanism of (preterm) labor.
Allergic Rhinitis
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Cysteinyl leukotrienes are a family of eicosanoid inflammatory mediators (LTC4, LTD4 and LTE4) produced in leukocytes, mast cells, eosinophils, basophils and macrophages by the oxidation of arachidonic acid by the enzyme arachidonate 5–lipoxygenase. Their effects are to cause bronchoconstriction, increase vascular permeability and attract inflammatory cells and as such are involved in the processes underlying asthma and allergic rhinitis.63 In the UK montelukast (a leukotriene receptor antagonist) is licensed for the treatment of allergic rhinitis associated with asthma. In studies it was found to be as effective as loratadine in reducing nasal symptoms but less effective than a topical nasal steroid.64 Combined use of cetirizine and montelukast was shown not to improve symptom control above each drug individually in one study65 but to be more effective when combined in another.66 There is a significant variation in responsiveness to LTRAs and a closely monitored trial of treatment may be useful in some patients. It now has a place in the updated ARIA treatment guidelines (Figure 91.3).
Control of blood vessels: intrinsic control
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
Leukotrienes are vasoactive eicosanoids produced from A A by the action of arachidonate 5-lipoxygenase (cf. COX) in leukocytes. They contribute to the inflammatory response by causing leukocyte margination-emigration and venular hyperpermeability, for example, the bronchial inflammation of asthma. Their gap-inducing action on venules is 1000-fold more potent than that of histamine. Leukotrienes can also cause vasoconstriction or dilatation, depending on the tissue.
Bioinformatics analysis of potential key ferroptosis-related genes involved in tubulointerstitial injury in patients with diabetic nephropathy
Published in Renal Failure, 2023
Li-Li Ma, Yu Bai, Wen-Hu Liu, Zong-Li Diao
In this study, six ferroptosis-related DEGs, ALOX5, NCF2, PTEN, CD44, DDIT3, and VEGFA, were identified as key genes. Arachidonate 5-lipoxygenase (5-LO), encoded by the ALOX5 gene, has recently been shown to play a central role in ferroptosis [39]. 5-LO is an essential enzyme that mediates lipid peroxidation by generating lipid peroxides [40], which is a critical feature of ferroptosis [41]. Numerous studies have shown that 5-LO is a target for ferroptosis, including in neurological disorders and renal failure [1,42–44]. Pharmacological inhibition of 5-LO by zileuton exhibited a neuroprotective role in glutamate-induced HT22 cells by blunting ferroptosis [42], while inhibiting 5-LO could also protect neurons from ferroptosis-related death in mice with hemorrhagic stroke via neutralizing lipid peroxides [43]. Overexpression of three selected ALOX isoforms (ALOX5, ALOX12, and ALOX15) in human embryonic kidney (HEK293) cells sensitized them to erastin-induced cell death [44]. Interference with 5-LO can alleviate inflammation and fibrosis in HG-induced renal mesangial cells [45]. Numerous studies have demonstrated that inflammation-related processes and immune cells are potentially involved in DN progression [46]. Leukotrienes (LTs) are a family of lipid mediators that function as pro-inflammatory mediators. LTs are synthesized in leukocytes from arachidonic acid, which is metabolized by 5-LO [47]. We therefore hypothesized that 5-LO might be a key molecule in the ferroptosis process in DN.
Nanosized silver, but not titanium dioxide or zinc oxide, enhances oxidative stress and inflammatory response by inducing 5-HETE activation in THP-1 cells
Published in Nanotoxicology, 2020
Wing-Lam Poon, Jetty Chung-Yung Lee, Kin Sum Leung, Harri Alenius, Hani El-Nezami, Piia Karisola
Gene expression of several enzymes involved in oxidation of PUFA were also found to be disrupted by n-Ag in the microarray analyses especially at 24 h. Phospholipase A2 isozymes are responsible for the hydrolytic release of sn-2 fatty acid (including AA) from membrane phospholipids and some of them were upregulated (PLA2G4C) by n/b-ZnO and especially by n-Ag, when compared to unexposed controls (Figure 4(A)). ALOX5 (arachidonate 5-Lipoxygenase, also known as 5-LOX, Figure 4(B)), which catalyzes the conversion of AA to 5-HpETE (the precursor of 5-HETE), and its activating protein, ALOX5AP (arachidonate 5-lipoxygenase-activating protein, also known as FLAP, Figure 4(C)) were down-regulated, whereas expression of the COX-2 gene (called also PTGS2) was found to be increased exclusively by n-Ag (Figure 4(D)).
Two acute myeloid leukemia patient subsets are identified based on the constitutive PI3K-Akt-mTOR signaling of their leukemic cells; a functional, proteomic, and transcriptomic comparison
Published in Expert Opinion on Therapeutic Targets, 2018
Ina Nepstad, Kimberley J. Hatfield, Elise Aasebø, Maria Hernandez-Valladares, Annette K. Brenner, Sushma Bartaula-Brevik, Frode Berven, Frode Selheim, Jørn Skavland, Bjørn Tore Gjertsen, Håkon Reikvam, Øystein Bruserud
We performed a proteomic comparison of AML cells with high (eight patients) and low (12 patients) constitutive PI3K-Akt-mTOR signaling. These patients should be regarded as an unselected subset; they represent all patients below 70 years of age that received intensive and potentially curative antileukemic treatment during a defined period (see also Supplementary Table 4). We used a two-sided Student’s t-test (homoscedastic two-sample t-test) to find proteins with a significantly different average abundance in the two groups. Furthermore, the relative difference (i.e. fold change) was statistically evaluated using Z-statistics [24]. We identified 83 proteins showing a statistically significant difference (p < 0.05) with both these approaches. The 33 proteins showing p < 0.01 in the t-test analysis or p < 0.0001 in the fold change analysis are listed (Table 3 upper part (A), Supplementary Table 6). Five of the proteins that were increased in the low phosphorylation subset are involved in lipid metabolism, including arachidonate 5-lipoxygenase activating protein (ALOX5AP) which is important for arachidonic acid metabolism. Five other proteins involved in cellular metabolism were increased in the high constitutive signaling group, including proteins important for amino acid and adenosine metabolism.