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Beneficial Effects of Omega-3 Fatty Acids on Cardiovascular Disease
Published in Catherina Caballero-George, Natural Products and Cardiovascular Health, 2018
Estela Guerrero De León, Mahabir Prashad Gupta, Juan Antonio Morán-Pinzón
Meanwhile, the actions of RvD1 are mediated by two G protein-coupled receptors (GPCR), ALX/FPR2 and GPR32, which also regulate specific microRNAs (miRNAs) and their target genes in new resolution circuits. Interaction with ALX/FPR2 signals could control infiltration of polymorphonuclear neutrophils (PMN) and stimulate macrophagocytosis of apoptotic PMNs (Chiang et al., 2006), while it is suggested that the GPR32 also plays a key role in mediating the effects of RvD1 on human macrophages (Schmid et al., 2016). Despite numerous findings that document the molecular actions associated with the anti-inflammatory effects of ω-3 PUFAs, crucial aspects of signaling mechanisms and downstream interactions remain to be elucidated.
Inflammation resolution and specialized pro-resolving lipid mediators in chronic rhinosinusitis
Published in Expert Review of Clinical Immunology, 2023
Peyton Z. Robinson, Daniel N. Frank, Vijay R. Ramakrishnan
SPMs initiate a variety of downstream pro-resolving effects through utilization of different receptors expressed in varied cell types. SPMs elicit much of their responses through G-coupled protein receptors (GPCRs) on innate immune cells. Current research indicates that E-series resolvins utilize the BLT1 and ERV1 receptors and D-Series resolvins utilize DRV/GPR32 and FPR2/ALX receptors [59,60]. ALX is expressed by leukocytes, epithelial cells, and platelets. Its activation results in limited release of tumor necrosis factors. The DRV1/GPR32 receptor is found on epithelial cells, where receptor activation is associated with wound healing. E-series resolvins act through the ERV1/ChemR23 receptor found in leukocytes, platelets, and dendritic cells [61]. The BLT1 receptor has only been found in neutrophils. RvE1 decreases LTB4 activity by also acting through the LTB4 receptor, BLT1 [62], preventing vital signaling pathways for LTB4 to continue the inflammatory response. Many of the SPMs uniquely bind to GPCRs, and utilize phosphorylation reactions rather than calcium signaling second messenger pathways, ultimately altering the cytoskeleton to direct cells toward pro-resolving activities [61]. In addition to independent pro-resolving activity, part of the SPM tissue response occurs through modulation or inhibition of other pro-inflammatory signaling pathways, such as the inhibition of leukotriene activity via RvE1 and the NF-kB pathway via RvD1 [62,63].
Macrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease
Published in Expert Opinion on Therapeutic Targets, 2021
Yaoyao Du, Lan Rong, Yuanhua Cong, Lan Shen, Ning Zhang, Bing Wang
Resolvins, a group of specialized proresolving mediators (SPMs) possess anti-inflammatory and pro-resolving actions [212]. According to the types of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) that are the precursors of resolvins, the resolvins family can be divided into E-series resolvins (RvE1, RvE2, and RvE3) derived from eicosapentaenoic (EPA) and D-series resolvins (RvD1, RvD2, RvD3,RvD4, and RvD5) that are derived from docosahexaenoic (DHA) acid [213,214]. Resolvins can induce specialized biological effects by binding to G protein-coupled receptors (GPCRs) [214]. For example, RvE1 and partial RvE2 can bind to ChemR23 on the surface of M1 macrophages to enhance the phagocytosis of apoptotic cells by macrophages and reduce the secretion of pro-inflammatory cytokines [215,216]. Furthermore, RvD5 and RvD3 can promote the polarization of M2 macrophages after activating GPR32 [214,217]. Although many animal experiments have confirmed that resolvins can play an active role in the process of inflammation regression, the related clinical studies are relatively scarce. At present, fish oil rich in ω-3 PUFAs has been proved to have the effect of alleviating inflammatory reaction in many clinical trials [218,219]. In addition, besides RvD and RvE, a variety of new series of resolvins were found in different stages of inflammatory reaction [220]. It provides a new idea for the treatment of inflammation-related diseases and resolvins are expected to become a novel anti-inflammatory drug.
Inflammation resolution and specialized pro-resolving lipid mediators in CNS diseases
Published in Expert Opinion on Therapeutic Targets, 2019
Pei Shang, Ying Zhang, Di Ma, Yulei Hao, Xinyu Wang, Meiying Xin, Yunhai Zhang, Mingqin Zhu, Jiachun Feng
SPMs function through a receptor-dependent signaling transduction pathway. SPMs were previously recognized as pro-inflammatory lipid mediators in acute inflammation because the analogies of PGs and LTs. However, Serhan et al. [40] demonstrated that SPMs had anti-inflammatory rather than pro-inflammatory properties in acute and chronic inflammation models. The most well-studied SPMs include LXA4, RvDs, RvEs, MaRs, and PD1. Six SPM receptors have been identified, which are all G protein-coupled receptors (GPCRs), including formyl peptide receptor type 2 (ALX/FPR2 or FPR2/3), D resolving receptor 1 (DRV1 or GPR32), D resolving receptor 2 (DRV2 or GPR18), E resolving receptor 1 (ERV1 or ChemR23), LTB4 receptor-1 (BLT1), and PD1 receptor (GPR37) [41,42]. Activation of SPM receptors introduces various protective effects for different cell types in neurological disorders (Figure 2). Functional differences among SPMs have not been illustrated currently. However, differences in the SPM biosynthetic process determined their interlaced timepoints of presence. For instance, in intestinal ischemia, LOX-dependent LXA4 always presented upon ischemia and decreased to normal levels 48 h later; however, high levels of the RvE1 precursor 18-HEPE were constantly sustained after 48 h, which was related to a sustained Cytochrome P450 function [43]. It is important to emphasize that SPMs are different from most anti-inflammatory drugs that always inhibit the production of inflammatory substances. On the contrary, SPMs actively induce the activation of the inflammation resolution pathway to clear the pathogens, which ultimately shortens the duration required for resolution and regeneration and initiates the healing process [44].