September 2022 GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome Infiltrating GPR84+ macrophages are significantly increased in the colonic mucosa of both the UC patients

September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages and NK cells. To exert their functions requiring high sensibility and specificity, T cells need to integrate different stimuli from the surrounding microenvironment. A finely tuned signalling compartmentalization orchestrated in dynamic platforms is an essential requirement for the proper and efficient response of these cells to distinct triggers. During years, several studies have depicted the pivotal role of the cytoskeleton and lipid microdomains in controlling signalling compartmentalization during T cell activation and functions. Here, we discuss mechanisms responsible for signalling amplification and compartmentalization in T cell activation, focusing on the role of CD28, chemokine receptors and the actin cytoskeleton. We also take into account the detrimental effect of mutations carried by distinct signalling proteins giving rise to syndromes characterized by defects in T cell functionality." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "The atypical chemokine receptor 1 (ACKR1) was discovered on erythrocytes as the Duffy blood group antigen ( Cutbush et al., 1950 ), also called Duffy-antigen/receptor for chemokines, or DARC ( Novitzky-Basso and Rot, 2012 ). Erythrocytes are terminally differentiated anuclear cells with no transcription and limited translation. Accordingly, within the erythroid lineage ACKR1 expression occurs first and is the highest in erythroblasts ( Duchene et al., 2017 ). Additionally, ACKR1 expression characterizes venular endothelial cells (ECs) ( Pruenster et al., 2009 ; Thiriot et al., 2017 ), including those lining bone marrow (BM) sinusoids ( Duchene et al., 2017 ). This well-established, distinctive pattern of cell expression has been directly challenged by a publication purporting ACKR1 expression in mouse BM by macrophages, but not erythroblasts and ECs, suggesting that macrophage ACKR1 engages its non-cognate ligand CD82 on hematopoietic stem cells (HSCs) to maintain their quiescence ( Hur et al., 2016 ). In light of the extensive literature, these findings have been particularly provocative, as this was the first description of ACKR1 expression by any leukocyte type and, if correct, would change current concepts of ACKR1 involvement in pathophysiology. The reported ACKR1 expression by macrophages in Hur et al. relied on using commercial anti-ACKR1 antibody FAB6695, which has neither been validated by the manufacturer nor by the authors. This prompted us to investigate the specificity of FAB6695 and scrutinize the apparent ACKR1 expression in BM macrophages" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein Coupled Receptors (GPCRs). GPR21 couples to the Gq family of G proteins and is expressed in macrophages. Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration. The aim of this study was to evaluate the role of GPR21 in human macrophages, analyzing (i) its involvement in cell migration and cytokine release and (ii) the consequence of its pharmacological inhibition by using the inverse agonist GRA2. THP-1 cells were activated and differentiated into either M1 or M2 macrophages. GPR21 expression was evaluated at gene and protein level, the signalling pathway was investigated by an IP1 assay, and cytokine release by ELISA. Cell migration was detected by the Boyden chamber migration assay, performed on macrophages derived from both the THP-1 cell line and human peripheral blood monocytes." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation "G protein-coupled receptor kinase type 2 (GRK2) and β-arrestin2 are representative proteins that regulate the transduction and trafficking of G protein-coupled receptor (GPCR) signaling. The kinase GRK2 and the multifunctional scaffolding protein β-arrestin2 are key integrated signaling nodes in various biological processes, and both of them regulate cell proliferation and promote cell invasion and migration. GRK2/β-arrestin2 play multiple roles in the pathological mechanisms of a wide range of diseases including heart failure, cancer, and inflammatory diseases. This review summarizes the roles of GRK2/β-arrestin2 in immune cell function and focuses on the pathological implications of GRK2/β-arrestin2 in various inflammatory diseases." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Bone remodeling is precisely regulated mainly by osteoblasts and osteoclasts. Although some G-protein coupled receptors (GPCRs) were reported to play roles in osteoblast function, little is known about the roles in osteoclasts. In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis. GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also called synaptamide). Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand. Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit osteoclastogenesis by affecting synaptamide/GPR110 signaling. But GPR110 knockout and subsequent rescue experiments revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA. These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis. Our study suggested that ligands of GPR110, such as synaptamide, might be a useful drug for osteoporotic patients." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 " Background and purpose: Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca2+ channels (VGCCs). Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, associate with elevated blood pressure; however, neither SVEP1 nor integrin α9β1 has reported roles in vasoregulation. We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Aims: The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor (PPAR) α/γ agonist saroglitazar, has been approved. Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction. " Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 TAS2R supports odontoblastic differentiation of human dental pulp stem cells in the inflammatory microenvironment " Background: Inflammatory microenvironment promotes odontoblastic differentiation in human dental pulp stem cells (hDPSCs), but the regulatory mechanisms remain unclear. In this study, we aimed to explore the role of TAS2R in odontoblastic differentiation of hDPSCs in the inflammatory microenvironment. Methods: Microarray analysis was performed to explore the differential mRNA profiles in inflammatory and healthy pulp tissues from the patients. hDPSCs isolated from the healthy pulp tissues were stimulated by LPS, TNFα and IL-6, respectively, to verify the effect of TAS2R. The expression markers related to odontoblastic differentiation of hDPSCs were observed by qPCR and chemical staining methods. TAS2R10 was overexpressed or silenced to observe the effect on odontoblastic differentiation of hDPSCs under LPS stimulation. The G protein and intracellular Ca2+ were detected, respectively, by qPCR and Fluo-4AM Ca2+ fluorescent probe." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation "Gut intraepithelial lymphocytes (IELs) are thought to calibrate glucagon-like peptide 1 (GLP-1) bioavailability, thereby regulating systemic glucose and lipid metabolism. Here, we show that the gut IEL GLP-1 receptor (GLP-1R) is not required for enteroendocrine L cell GLP-1 secretion and glucose homeostasis nor for the metabolic benefits of GLP-1R agonists (GLP-1RAs). Instead, the gut IEL GLP-1R is essential for the full effects of GLP-1RAs on gut microbiota. Moreover, independent of glucose control or weight loss, the anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectively restrain local and systemic T cell-induced, but not lipopolysaccharide-induced, inflammation. Such effects are mediated by the suppression of gut IEL effector functions linked to the dampening of proximal T cell receptor signaling in a protein-kinase-A-dependent manner. These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealing mechanisms linking GLP-1R activation in gut IELs to modulation of microbiota composition and control of intestinal and systemic inflammation." Read more at the source #DrGPCR #GPCR #IndustryNews

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The molecular mechanisms N. meningitidis employ to manipulate the immune system, translocate the mucosal

selection Research will be focused on up to 15 novel small molecule candidates across oncology and immunology collaboration and license agreement to develop up to 15 novel small molecule candidates across oncology and immunology novel bispecific small molecule candidate capable of targeting two distinct targets in inflammation and immunology

the Formation of a Scientific Advisory Board comprising international leaders in GPCRs pharmacology, immunology

GPCR Symposium for the year on GPCRs in Immunology and Oncology! Indirect Pathway Striatal Spiny Neurons to Brain-Derived Neurotrophic Factor GPCRs in Oncology and Immunology

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They participate in the activation, chemotaxis and recruitment of multiple immunological cells such as

Modern drug development approaches include a range of techniques leveraging structural biology, immunology

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Obesity, immunological diseases and endocrine metabolic diseases are high-risk factors for the development

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GPCRs in Oncology and Immunology Ovarian cancer G protein-coupled receptor 1 (OGR1) deficiency exacerbates

blood-brain barrier regulates sleep via Moody G protein-coupled receptor signaling GPCRs in Oncology and Immunology

Immunoblotting approach was used to analyze signaling involved in fentanyl’s action focusing on EGFR.