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The Inflammatory Response: A Bridge Between The Constitutive and Inducible Systems
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
In addition to the vasoactive amines, histamine and serotonin, there are other vasoactive hormones released at the site of an inflammatory response. They include the prostaglandins and leukotrienes. The prostaglandins and leukotrienes are lipid hormones. They are derived from arachidonic acid which is cleaved from the membrane phospholipids by phospholipase A2 (Figure 4.2). The phospholipase is activated by substances that damage cell membranes. After release, the arachidonic acid is oxygenated by one or the other of two enzyme systems. These are the cyclooxygenase system, the actions of which result in the production of the prostaglandins, and the lipooxygenase system, the actions of which result in the production of the leukotrienes. A large number of different prostaglandins have been described. The major prostaglandins produced are PGE1, PGE2, PGF2a, prostacyclin (PG12), and Thromboxane A2. The leukotrienes produced include LTB4, LTC4, LTD4, LTE4, and LTF4.
Macronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Phospholipids also known as phosphoglycerides are fat compounds and have a glycerol backbone linked to a hydrophilic phosphate group, and two hydrophobic fatty-acid molecules. The phosphate group can be coupled with a nitrogen-containing compound and is water-soluble (67, 69, 114–115). So, phospholipids are amphipathic molecules, consisting of two hydrophobic fatty acid chains and a phosphate-containing hydrophilic head group, forming the fundamental building blocks of all cell membranes (115–116). By this special structure, phospholipids are amphiphilic compounds; they are both water-soluble and liposoluble. Because their fatty acid tails are insoluble in water, phospholipids spontaneously form stable bilayers in aqueous solutions, with the hydrophobic tails (fatty acids) buried in the interior of the cell membrane and the polar head groups (phosphates exposed to water present in the cell) (115). In blood and body fluids, phospholipids form structures in which fatty acids like omega-3, omega-6 fatty acids, cholesterol, and so on, are enclosed and transported throughout the bloodstream due to their amphiphilic nature (67). In cells, phospholipases hydrolyze phospholipids by releasing the transported fatty acids.
Oral Corticosteroids
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Lipocortins (annexins) inhibit the activity of phospholipase A2. Phospholipase A2 releases arachidonic acid from phospholipids for production of prostanoids and leukotrienes, which produces an inflammatory response. Corticosteroids act as anti-inflammatories by stimulating the production of lipocortins. Corticosteroids also inhibit formation of interleukin-1 by inhibiting mRNA. By altering arachidonic acid metabolism and reducing interleukin-1 formation, corticosteroids produce immunosuppressive, anti-inflammatory, and anti-mitogenic effects [4,5].
Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Fabrice Pagniez, Nicolas Lebouvier, Young Min Na, Isabelle Ourliac-Garnier, Carine Picot, Marc Le Borgne, Patrice Le Pape
Candida spp. are known to produce several types of phospholipases such as phospholipase B and phospholipase A which were detected in culture supernatant16,17. The virulence of Candida strains in G. mellonella is related to the quantity of phospholipases production18 and strains isolated from symptomatic women with vulvovaginal candidiasis exhibit high level of phospholipase activity19. Phospholipase B has been described as a pathogenic factor that contributes to host membrane degradation and penetration of C. albicans pseudohyphae20. Intracellular phospholipases, identified as phospholipases A, have been localised at the site of bud formation21. Triglyceride lipases with phospholipase A2-like activity (patatin-like homologs) have been described in Saccharomyces and Candida22. Already known function of this phospholipase is hydrolysis of fatty acids for membrane formation and sporulation. Since indole derivatives have been reported as inhibitors of phospholipase A2 activity10,23 our 2-dichlorophenyl-3-triazolyl-1-indolyl-propan-2-ol derivative (8 g) could be of interest to inhibit this enzyme activity.
PLCG2 promotes hepatocyte proliferation in vitro via NF-κB and ERK pathway by targeting bcl2, myc and ccnd1
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Donghui Ma, Fang Lian, Xiaobai Wang
It is now well established that the metabolism of phospholipase plays an important role in a wide variety of cellular functions. The hydrolysis of phosphatidylinositol 4,5-bisphosphate by a specific phospholipase C (PLC) to two important second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), is one of the earliest key events triggered by a large number of extracellular signalling molecules. This effector role of PLC enzymes in signal transduction pathways has made them a subject of extensive research [1–4]. PI-PLC molecules have been found in a broad spectrum of organisms including bacteria, simple eukaryotes, plants and animals [5–9]. Studies of PI-PLC enzymes have included their catalytic properties, structure determination and, most extensively, their regulation through different signalling pathways [10] leading to different activities including proliferation, cell apoptosis, transformation, and tumor growth.
Evaluation of anti-inflammatory impact of dexamethasone-loaded PCL-PEG-PCL micelles on endotoxin-induced uveitis in rabbits
Published in Pharmaceutical Development and Technology, 2019
Mitra Alami-Milani, Parvin Zakeri-Milani, Hadi Valizadeh, Shahram Sattari, Sara Salatin, Mitra Jelvehgari
Corticosteroids are the most common medication used to reduce the inflammatory symptoms in uveitis (Behar-Cohen et al. 1997). Among the corticosteroids, dexamethasone (DEX) is one of the most potent; with an anti-inflammatory activity that is thirty-fold greater than that of cortisol and six-fold greater than triamcinolone (Herrero-Vanrell et al. 2011; Bandello et al. 2015). The anti-inflammatory function of corticosteroids has been ascribed to a group of phospholipase A2 inhibitory proteins, conjointly called lipocortin (Wallner et al. 1986). Phospholipase A2 is an enzyme which acts on the cell membrane and releases arachidonic acid from membrane-bound phospholipids (Tamby et al. 1993). Application of DEX up-regulates the synthesis of lipocortin, thereby reducing the production of arachidonic acid metabolites (Lima et al. 2017).