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PMC:7781431 / 13725-24078 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T125 0-14 Sentence denotes SPMs receptors
T126 15-78 Sentence denotes Herein, we briefly describe each known SPMs receptors (Fig. 2).
T127 79-303 Sentence denotes Previous studies have demonstrated that pro-resolving activities of SPMs occur through activation of one or more G protein-coupled receptors (GPCRs), suitable receptors for several types of SPMs have not yet been identified.
T128 304-506 Sentence denotes Four GPCRs have been reported as receptors for RvD1 and RvE1; however, it has not been determined whether other Rvs and PDs such as RvE2, RvE4, RvD2, RvD3, PDs, and MaRs act on these GPCRs (Arita et al.
T129 507-540 Sentence denotes 2005, 2007; Krishnamoorthy et al.
T130 541-547 Sentence denotes 2010).
T131 548-716 Sentence denotes For recent and specific physiological actions of these receptors and research data in KO mice, we would like to refer to other reviews and references there (Park et al.
T132 717-732 Sentence denotes 2020; Im 2012).
T133 734-753 Sentence denotes Chemerin receptor 1
T134 754-945 Sentence denotes Chemerin receptor 1 (chemerin1, ChemR23, or ERV1) is expressed on a wide range of immune cells, including monocytes, macrophages, natural killer cells, bone marrow cells, and dendritic cells.
T135 946-1032 Sentence denotes Besides, ERV1 has been identified in adipocytes and endothelial cells (Luangsay et al.
T136 1033-1039 Sentence denotes 2009).
T137 1040-1146 Sentence denotes ERV1 was initially classified as an orphan GPCR with homology to the formyl peptide receptor (Gantz et al.
T138 1147-1211 Sentence denotes 1996) and the anaphylatoxin C3a and C5a receptors (Samson et al.
T139 1212-1323 Sentence denotes 1998) until recently when it was discovered to be a receptor for the chemotactic protein chemerin (Meder et al.
T140 1324-1330 Sentence denotes 2003).
T141 1331-1471 Sentence denotes In addition to chemerin, RvE1 was identified as a second endogenous agonist through a screening program against the GPCR panel (Arita et al.
T142 1472-1478 Sentence denotes 2007).
T143 1479-1647 Sentence denotes ERV1 (chemokine like receptor 1, also known as CMKLR1) is a receptor for RvE1, which has been shown to bind more strongly than chemerin (a peptide ligand) (Arita et al.
T144 1648-1669 Sentence denotes 2005; Wittamer et al.
T145 1670-1676 Sentence denotes 2004).
T146 1677-1832 Sentence denotes ERV1 overexpressing mice showed a large increase in phagocytosis upon decreased neutrophil inhibition and decreased neutrophil infiltration (Herrera et al.
T147 1833-1839 Sentence denotes 2015).
T148 1840-1942 Sentence denotes Also, RvE2 is a partial agonist compared to RvE1 in CHO-chemerin1 β-arrestin recruitment (Isobe et al.
T149 1943-1950 Sentence denotes 2012a).
T150 1951-2086 Sentence denotes However, since there is no additional information on this ligand, further investigation of potential ligand-receptor pairs is required.
T151 2088-2141 Sentence denotes N-formyl peptide receptor 2/LX A4 receptor (FPR2/ALX)
T152 2142-2297 Sentence denotes Originally FPR2 was classified as an FPR receptor due to its activation by the low-affinity endogenous agonist N-formyl methionyl peptide (fMLP) (Ye et al.
T153 2298-2304 Sentence denotes 1992).
T154 2305-2543 Sentence denotes The receptor was reclassified as FPR2/ALX, as LXA4 exhibited the highest affinity of all FPR2/ALX endogenous agonists through screening of various receptor ligands using radiolabelled [3H]-LXA4 and subsequent GTPase activity (Fiore et al.
T155 2544-2562 Sentence denotes 1994; Brink et al.
T156 2563-2569 Sentence denotes 2003).
T157 2570-2696 Sentence denotes Binding of LXA4 leads to the stimulation of monocyte chemotaxis, macrophage differentiation, and efferocytosis (Maderna et al.
T158 2697-2727 Sentence denotes 2010; Maddox and Serhan 1996).
T159 2728-2852 Sentence denotes LXA4 also reduces the adaptive immune response by reducing memory B cell antibody production and proliferation (Ramon et al.
T160 2853-2859 Sentence denotes 2014).
T161 2860-3030 Sentence denotes Endogenous and exogenous lipids, peptides, and proteins have been shown to bind and activate FPR2/ALX to produce inflammatory and anti-inflammatory effects (Takano et al.
T162 3031-3050 Sentence denotes 1997; Cooray et al.
T163 3051-3057 Sentence denotes 2013).
T164 3058-3217 Sentence denotes Both the LXs and Rvs families, including LXA4, AT-LXA4 (15-epi-LXA4), RvD1, AT-RvD1 (17-epi-RvD1), and Annexin A1 (ANXA1) activate receptors with high potency.
T165 3218-3357 Sentence denotes On the other hand, endogenous antagonists, including serum amyloid A (SAA) and cathelicidin (LL-37) have been identified (Bozinovski et al.
T166 3358-3374 Sentence denotes 2012; Wan et al.
T167 3375-3381 Sentence denotes 2011).
T168 3383-3388 Sentence denotes GPR18
T169 3389-3487 Sentence denotes GPR18 was discovered as a receptor for RvD2 through GPCR-β-arrestin-based screening (Chiang et al.
T170 3488-3556 Sentence denotes 2015), and the receptor was referred to as DRV2/GPR18 (Chiang et al.
T171 3557-3570 Sentence denotes 2017, 2019a).
T172 3571-3622 Sentence denotes Besides, several other ligands activate DRV2/GPR18.
T173 3623-3938 Sentence denotes These include endogenous ligands such as N-arachidonylglycine (NAGly), anandamide, a metabolite of the endocannabinoid anandamide, synthetic ligands such as abnormal-cannabidiol (Abn-CBD), and O-1918, a partial agonist, which can be used as a pharmacological tool to inhibit DRV2/GPR18 signalling (Offertaler et al.
T174 3939-3957 Sentence denotes 2003; Kohno et al.
T175 3958-3964 Sentence denotes 2006).
T176 3965-4042 Sentence denotes GPR18 is abundantly expressed in PMNs, monocytes and macrophages (Wang et al.
T177 4043-4049 Sentence denotes 2014).
T178 4050-4416 Sentence denotes In addition to the resolution of inflammation, while GPR18 has low structural similarity to the cannabinoid receptors CB1, CB2, and GPR55, it responds to endogenous and synthetic cannabinoid ligands including n-arachidonoyl ethanolamine (AEA), 2-arachidonoyl glycerol (2-AG), Δ9-tetrahydrocannabinol (Δ9-THC), and, arachidonoylcyclopropylamide (ACPA) (McHugh, 2012).
T179 4417-4680 Sentence denotes Also interestingly, GPR18 is structurally very similar to EBV-induced receptor 2 (EBI2), whose expression is increased more than 20 times in Epstein-Barr virus (EBV) infected cells, and is a GPCR receptor clustered together in the 13q32 (Rosenkilde et al., 2006).
T180 4682-4687 Sentence denotes GPR32
T181 4688-4814 Sentence denotes GPR32 is primarily expressed in human PMN, monocytes, adipose tissue and vascular endothelial cells (Sansbury and Spite 2016).
T182 4815-5043 Sentence denotes RvD1 was identified as a potential agonist due to the activation of GPR32, where [3H]-RvD1 binds to human leukocytes and significantly lowers TNF-α-stimulated NF-κB signalling in GPR32 overexpressing cells (Krishnamoorthy et al.
T183 5044-5050 Sentence denotes 2010).
T184 5051-5187 Sentence denotes Although RvD1 has a higher affinity for GPR32 than FPR2/ALX, its interaction with GPR32 has not been extensively studied (Norling et al.
T185 5188-5194 Sentence denotes 2012).
T186 5195-5310 Sentence denotes This could be since GPR32 exists as a pseudogene in rodents, which makes animal testing in principle inappropriate.
T187 5311-5505 Sentence denotes Treatment of inflammatory macrophages expressing GPR32 with RvD1 enhanced the pro-resolving phenotype to increase phagocytosis and decrease the secretion of inflammatory cytokines (Schmid et al.
T188 5506-5512 Sentence denotes 2016).
T189 5513-5637 Sentence denotes Also, GPR32 was also involved when during the inhibition of the EMT phenomenon of lung cancer cell lines by RvD1 (Lee et al.
T190 5638-5644 Sentence denotes 2013).
T191 5645-5784 Sentence denotes Additionally, RvD3, AT-RvD3, and RvD5 have all been shown to activate GPR32 in a recombinant system of β-arrestin recruitment (Dalli et al.
T192 5785-5805 Sentence denotes 2013b; Chiang et al.
T193 5806-5812 Sentence denotes 2012).
T194 5813-5885 Sentence denotes These facts suggest the potential redundancy of ligands acting on GPCRs.
T195 5887-5892 Sentence denotes GPR37
T196 5893-6063 Sentence denotes GPR37 or Parkin-related endothelin-like receptor (Pael-R) was originally discovered through genomic library screening to find new neuropeptide receptors (Marazziti et al.
T197 6064-6070 Sentence denotes 1997).
T198 6071-6221 Sentence denotes The GPR37 receptor is primarily expressed in the brain and is associated with neurological disorders such as Parkin’s disease and autism (Lopes et al.
T199 6222-6228 Sentence denotes 2015).
T200 6229-6382 Sentence denotes Mutations within GPR37 affect various autism spectrum disorders, regulation of dopamine reuptake and oligodendrocyte differentiation (Fujita-Jimbo et al.
T201 6383-6405 Sentence denotes 2012; Marazziti et al.
T202 6406-6423 Sentence denotes 2007; Yang et al.
T203 6424-6430 Sentence denotes 2016).
T204 6431-6629 Sentence denotes PD1 is considered as a ligand for GPR37 because it induced a significant increase in intracellular calcium in HEK293 cells overexpressing GPR37 and murine peritoneal-derived macrophages (Bang et al.
T205 6630-6636 Sentence denotes 2018).
T206 6637-6869 Sentence denotes Based on the fact that Gpr37-/- mice exhibited increased apoptosis and infarct size, it has recently been suggested that GPR37 is also involved in cell damage protection and inflammation after ischemic stroke (McCrary et al., 2019).
T207 6870-7086 Sentence denotes However, due to its clear role in the central nervous system (CNS), the development of a therapeutic agent targeting GPR37 requires a balance between the effect on the central nervous system and therapeutic benefits.
T208 7088-7104 Sentence denotes Leukotriene BLT1
T209 7105-7361 Sentence denotes BLT1 has also been shown to be a receptor for RvE1 although its clone, high-affinity leukotriene B4 (LTB4) is a potent lipid inflammatory chemoattractant, inducing T helper cell chemotaxis and early effector T cell recruitment through BLT1 (Yokomizo et al.
T210 7362-7380 Sentence denotes 1997; Arita et al.
T211 7381-7387 Sentence denotes 2007).
T212 7388-7606 Sentence denotes BLT1 shares 21% sequence identity with chemerin1; while this value is relatively low, selective BLT1 antagonist U-75,302 has been demonstrated to replace the binding of [3H]-RvE1 to the human PMN membrane (Arita et al.
T213 7607-7613 Sentence denotes 2007).
T214 7614-7796 Sentence denotes Besides, although RvE1 is 100 times less potent than LTB4, it inhibited adenylate cyclase activity and induced intracellular calcium mobilization in HEK293 cells overexpressing BLT1.
T215 7797-7996 Sentence denotes These data indicate the role of RvE1 in reducing BLT1-induced inflammation by RvE1 acting as a partial agonist that competes with LTB4-mediated NF-κB activation and calcium mobilization (Arita et al.
T216 7997-8003 Sentence denotes 2007).
T217 8004-8208 Sentence denotes Activation of BLT1 by RvE1 also serves as a feedback mechanism for other SPMs, including increased production of LXA4 in the FPR2/ALX-mediated resolution of allergic pulmonary inflammation (Haworth et al.
T218 8209-8215 Sentence denotes 2008).
T219 8216-8434 Sentence denotes RvE2 was identified as an additional BLT1 agonist, and the β-arrestin assay showed that RvE2 blocked LTB4-mediated β-arrestin signalling with similar efficacy to RvE1, indicating direct competition with LTB4 (Oh et al.
T220 8435-8441 Sentence denotes 2012).
T221 8442-8570 Sentence denotes Various pro-resolving roles of RvE2 have been proposed, including regulation of PMN infiltration and IL-10 production (Oh et al.
T222 8571-8577 Sentence denotes 2012).
T223 8578-8716 Sentence denotes However, while RvE1 promotes NADPH oxidase-mediated ROS production through the BLT1, RvE2 and RvE3 do not exhibit this effect (Unno et al.
T224 8717-8723 Sentence denotes 2018).
T225 8725-8762 Sentence denotes Activation of other receptors by SPMs
T226 8763-8833 Sentence denotes A few studies have reported the possibility of other GPCR involvement.
T227 8834-8942 Sentence denotes Among them, GPR101 mediates the pro-resolving effects of RvD5n-3 DPA in arthritis and infection (Flak et al.
T228 8943-8949 Sentence denotes 2020).
T229 8950-9042 Sentence denotes Besides, SPMs have been reported to activate non-GPCRs receptors, such as nuclear receptors.
T230 9043-9229 Sentence denotes In a dose-dependent manner, PD1 enhances PPARγ transcriptional activation reporter activity in human neuron-glia (HNG) cells co-transfected with hPPARγ-GAL4 and MH100-tk-Luc (Zhao et al.
T231 9230-9236 Sentence denotes 2011).
T232 9237-9354 Sentence denotes This suggests that PD1 is capable of enhancing the peroxisome proliferator-activated receptor gamma (PPARγ) (Fig. 2).
T233 9355-9453 Sentence denotes The transcriptional activity of PPARγ was significantly increased after treatment with 100 nM PD1.
T234 9454-9685 Sentence denotes RvD1 was also assumed to be a ligand for PPARγ and inhibited IκBα degradation and NF-κB p65 nuclear translocation in an LPS-induced lung injury model, which was partially reversed by the PPARγ inhibitor GW9662 (Fig. 2) (Liao et al.
T235 9686-9692 Sentence denotes 2012).
T236 9693-9808 Sentence denotes Recently, it has been reported that LXA4 binds to the nuclear aryl hydrocarbon receptor (AhR) (Fig. 2) (Asha et al.
T237 9809-9815 Sentence denotes 2020).
T238 9816-9878 Sentence denotes A GPCR that acts directly on MaR1 has not yet been identified.
T239 9879-10201 Sentence denotes However, MaR1 blocks TRPV1-mediated currents in neurons, acts as a ligand for the retinoid-associated orphan receptor α (RORα), and inhibits TLR4 signalling (Fig. 2) (Park 2015), Chiang et al. found that MaR1 can activate LGR6, a member of the glycoprotein hormone receptor subfamily of rhodopsin-like GPCRs (Chiang et al.
T240 10202-10345 Sentence denotes 2019b), which initiates cAMP, impedance changes, and stimulate an innate immune response against PMNs, monocytes and macrophages (Chiang et al.
T241 10346-10353 Sentence denotes 2019b).