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Lipidomic Insight into Membrane Remodeling in Aging and Neurodegenerative Diseases
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Figure 7.6 clearly shows that an uncontrolled increase in 4-HNE generation may interfere with proapoptotic signaling and lead to the development of pathological conditions [50]. In contrast to ARA, the ω-3 LC-PUFAs, such as EPA, DPA, and DHA, can be metabolized to anti-inflammatory mediators [51]. However, the ARA-derived lipoxins are an exception and exert anti-inflammatory, pro-resolution bioactions [52,53].
Eicosanoids and Hypertension in Pregnancy
Published in Murray D. Mitchell, Eicosanoids in Reproduction, 2020
Scott W. Walsh, Valerie M. Parisi
The lipoxins share some of the same biological effects of the prostaglandins, HETEs, and LTs, but chemically they are distinct molecules. Lipoxin A induces arteriolar dilation, but does not affect micro vascular permeability, as does LTC4, or leukocyte adherence to venular endothelium, as does LTB4.13,14 Lipoxin A stimulates superoxide anion generation without provoking aggregation, causes chemotaxis, and possesses spasmogenic activities like the HETEs and LTs. Lipoxin A elicits long-lasting contractions of guinea pig lung strips, but, unlike LTC4, it does not stimulate contraction of the guinea pig ileum. Lipoxins A and B inhibit human natural killer cell activity, whereas HETEs and LTs do not affect natural killer cell cytotoxicity. Furthermore, lipoxins may serve as important intracellular mediators. Lipoxin A is a potent activator of protein kinase C, even more potent than diacylglyceride or arachidonic acid. Thus, lipoxins display patterns of physiological effects that are distinct from prostaglandins, thromboxanes, HETEs, or LTs.
Infection-driven periodontal disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Thomas E. Van Dyke, Mike Curtis
Lipoxins are the product of lipoxygenase and lipoxygenase interactions through transcellular biosynthetic pathways. Experimental evidence suggests that as an inflammatory lesion matures, the lipoxygenase product of one cell type (the product of the platelet 12-LO: 12-hydroxytetraenoic acid) is further metabolized by a myeloid cell 5-LO to produce lipoxin A4. The known lipoxin synthetic pathways are illustrated in Figure 29.3. LXA4 binds to different inflammatory cells to produce both anti-inflammatory and proresolution actions driving resolution of inflammation. LXA4 binding to FPRL receptors on inflammatory neutrophils inhibits chemotaxis, superoxide generation, and secretion of pro-inflammatory and proteolytic molecules, including PGE2, and induces neutrophil apoptosis. Concurrently, LXA4 is chemotactic for nonphlogistic recruitment of mononuclear phagocytes; the resolving monocyte/macrophage exhibits enhanced phagocytosis of bacteria and apoptotic neutrophils but does not secrete pro-inflammatory mediators. In the context of periodontal disease, there is detectable LXA4 in the gingival crevicular fluid of periodontitis patients, albeit at insufficient concentrations to exert clinical actions. These observations have suggested that periodontal diseases, and other inflammatory diseases, are characterized by a failure of resolution pathways in addition to, or instead of, overproduction of pro-inflammatory signals.
Silicone hydrogel contact lenses retain and document ocular surface lipid mediator profiles
Published in Clinical and Experimental Optometry, 2023
Karsten Gronert, Arnav Modi, Kaleb Asfaha, Sharon Chen, Elizabeth Dow, Scott Joslin, Mike Chemaly, Zohra Fadli, Leilani Sonoda, Bailin Liang
Marked differences in PUFA and hydroxy-PUFA were observed among individuals and the silicone hydrogel lens (senofilcon A) and modified- silicone hydrogel lens (Figures 3 and 4). Specifically, arachidonic acid and docosahexaenoic acid levels in modified-silicone hydrogel lenses were significantly lower than that in silicone hydrogel lenses by 45% and 32%, respectively (T-test, p < 0.05, Figure 3B). There were no significant differences (T-test, p > 0.05) in eicosapentaenoic acid levels among the two lens types. 5-hydroxyeicosatetraenoic, 12-hydroxyeicosatetraenoic and 15-hydroxyeicosatetraenoic levels were lower by 83%, 38% and 58%, respectively in modified-silicone hydrogel compared to silicone hydrogel. However, this difference was not statistically significant (T-test p > 0.05) due to variance of data points (Figure 3C). There were no serious or significant adverse events for any of the 57 subjects that used silicone hydrogel or modified-silicone hydrogel lenses. Adverse event endpoints included burning/stinging cloudy-blurry-hazy vision, dryness, grittiness-foreign body sensation, itchiness-scratchiness and redness. However, there were marked subject-specific lipid mediator profiles, namely, 12% and 18% of subjects had significant levels of lipoxin A4 and leukotriene B4 retained in their lenses (Table 1, Figure 4).
Impact of resolvin mediators in the immunopathology of diabetes and wound healing
Published in Expert Review of Clinical Immunology, 2021
David Shofler, Vikrant Rai, Sarah Mansager, Kira Cramer, Devendra K. Agrawal
Like resolvins, lipoxins are endogenous anti-inflammatory, pro-resolving molecules secreted by neutrophils and macrophages and play a crucial role in attenuating chronic inflammation and tissue injury. Lipoxins are synthesized from arachidonic acid in platelets, neutrophils, erythrocytes, and reticulocytes. Lipoxins regulate innate and adaptive immune responses and modulate the function of immune cells, including neutrophils, macrophages, T-, and B-cells. Additionally, lipoxins regulate the expression of many inflammatory genes and transcription factors including NF-κB, activator protein (AP)-I, nerve growth factor (NGF), and peroxisome proliferator-activated receptor (PPAR)-γ [16,17]. The anti-inflammatory and pro-resolution effect of lipoxins is mediated by their binding to G protein-coupled N-formyl peptide receptor 2 (ALX/FPR2), G protein-coupled receptor 32 (GPR 32), estrogen receptor, high-affinity cysteinyl leukotriene receptor, and aryl hydrocarbon receptors (reviewed in [16]). Lipoxins help recruit neutrophils at the site of inflammation and later help clear neutrophils from the site of inflammation, roles that help transform the inflammatory phase to the resolution phase. Lipoxins also regulate the recruitment, phagocytosis, and phenotypic conversion of macrophages to the site of inflammation, aiding in the resolution of inflammation. The anti-inflammatory effect of lipoxins is also mediated by regulating the secretion of pro-inflammatory cytokines, including TNF-α and IL-1β [16,17].
Asthma pharmacotherapy: an update on leukotriene treatments
Published in Expert Review of Respiratory Medicine, 2019
Hoang Kim Tu Trinh, So-Hee Lee, Thi Bich Tra Cao, Hae-Sim Park
Blockade of 5-LO enzymatic activity is beneficial for reducing LT synthesis, which induces vascular permeability and bronchoconstriction as well as LTB4-dependent pathway [33]. Nevertheless, it is unclear whether 5-LO inhibitors blocked the production of anti-inflammatory metabolites such as lipoxins. To date, among 5-LO inhibitors such as atreleuton (VIA-2291), MK-0633, PF-4,191,834, naproxen and flavocoxid, only zileuton is approved in clinical trials. Zileuton inhibits 5-hydroxyeicosatetranenoic acid synthesis, neutrophils and LTB4 biosynthesis, but it showed hepatic toxicity and adverse pharmacokinetic effects [34]. In patients with bronchial asthma, the robust effect of zileuton occurs 2 days after drug administration, but not immediately [11]. With increasing LTRA use, there is the need to develop novel 5-LO inhibitors.