G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation

Cheng, Huijuan; Guo, Pengfei; Su, Tiantian; Jiang, Chunru; Zhu, Zhenduo; Wei, Wei; Zhang, Lingling; Wang, Qingtong

doi:10.1016/j.cellsig.2022.110337

Cited by 12 publications

(10 citation statements)

References 201 publications

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“…To elucidate the mechanism by which HRH1 regulates the p38MAPK signaling pathway, we investigated the crosstalk between HRH1 and the G protein-coupled receptor kinase type 2 (GRK2), which has been identified as a vital protein that regulates the transduction and trafficking of G protein-coupled receptors (GPCR) signaling ( 27 ). In addition, p38MAPK is negatively regulated by GRK2 ( 28 ).…”

Section: Resultsmentioning

confidence: 99%

Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis

Guo

et al. 2022

mBio

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Once engulfed in macrophage phagosomes, M. tuberculosis adopts various strategies to take advantage of the host environment for its intracellular survival. Histamine is an organic nitrogen-containing compound that mediates a plethora of cellular processes via different receptors, but the crosstalk mechanism between M. tuberculosis and HRH1 in macrophages is not clear.

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Section: Resultsmentioning

confidence: 99%

Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis

Guo

et al. 2022

mBio

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“…However, a prior study suggested that the activation of beta2-adrenergic receptors (GPCRs) can modulate GRK2 ubiquitination and proteolysis, resulting in the rapid degradation 28 . Moreover, G protein-coupled receptor kinase 2 (GRK2) has been found to be involved in the regulation of multiple biological processes such as angiogenesis, metabolism, vasodilatation, immunity, and inflammation 26,29 . Moreover, GRK2 is implicated in the progression and pathogenesis of multiple diseases www.nature.com/scientificreports/ including autoimmune, fibrotic, and liver disorders 27,30,31 .…”

Section: Discussionmentioning

confidence: 99%

Endothelin receptor B enhances liver injury and pro-inflammatory responses by increasing G-protein-coupled receptor kinase-2 expression in primary biliary cholangitis

Gong

et al. 2022

Sci Rep

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Severe diseases like cirrhosis and liver failure can be developed from primary biliary cholangitis (PBC). Endothelin-2 (EDN2) and endothelin receptor B (EDNRB) are related to the pathogenesis of PBC. However, the roles of EDN2 and EDNRB in PBC-related liver injury and inflammation along with molecular mechanisms are poorly defined. In this study, histopathologic alterations of liver tissues were assessed through hematoxylin–eosin staining. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), and γ-Glutamyltranspetidase (GGT) (4 liver function indexes) serum levels were detected with corresponding activity assay kits. Also, we determined the levels of M2 subtype anti-mitochondrial antibody (AMA-M2), interferon-gamma (IFN-γ), and tumor-necrosis factor alpha (TNFα) in serum with ELISA assay. Later, RT-qPCR assay was used to measure the expression of genes at mRNA levels, while western blotting and immunohistochemical techniques were used to detect protein levels of genes. Our results showed that the liver tissues of PBC patients and mice presented with severe hepatocyte injury and inflammatory cell infiltration as well as destruction of intrahepatic small bile ducts. ALP, AST, ALT, GGT, AMA-M2, IFN-γ, and TNF-α serum levels were higher in PBC patients and mice. Besides, EDN2 and EDNRB were highly expressed in serums and livers of PBC patients and mice. EDNRB potentiated PBC-related liver injury and pro-inflammatory responses, as evidenced by observation of serious liver pathologic injury and increased serum levels of ALP, AST, ALT, AMA-M2, IFN-γ, and TNF-α in PBC mice following EDNRB overexpression. EDNRB overexpression or activation via its agonist IRL-1620 TFA triggered liver injury and pro-inflammatory responses, increased GRK2 expression and induced NF-κB expression and activation in wild-type mice. EDNRB knockdown or inhibition by Bosentan alleviated liver damage and inflammation, reduced GRK2 expression, and inhibited NF-κB in PBC mice. These findings suggested EDNRB loss or inhibition weakened liver injury and pro-inflammatory responses by down-regulating GRK2 and inhibiting the NF-κB pathway in PBC mice.

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“…A study has shown that Chemokine activities are mediated through G-protein coupled receptors which play a role in inflammatory responses [65]. We also noticed that the major putative targets were involved in the Interleukin-10 signaling pathways which regulate the anti-inflammatory cytokine, and they play a crucial role in preventing the inflammatory and autoimmune diseases [66].…”

Section: Gene Ontology and Pathway Enrichment Analysismentioning

confidence: 93%

An Efficient Weighted Network Centrality Approach for Exploring Mechanisms of Action of the RP-RB Herbal Formula for Treating Rheumatoid Arthritis

Ochieng

Dombi

Hussain

2022

Preprint

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Aim : This study presents an efficient weighted network centrality measureapproach and its application in network pharmacology for exploring mechanismsof action of the Ruellia prostrata (RP) and Ruellia bignoniiflora (RB) herbalformula for treating rheumatoid arthritis. Method: A tripartite network of RP-RB compositive compound-knowntherapeutic targets-putative target genes was first built. The interconnectivityscore was used to prioritizes network candidate network components based ontheir overall connectivity with shared neighborhood network components. A newinterconnectivity based weighted centrality score calculated from traditionalnetwork centrality measure was used identify and explore relationships of themajor network components. The functionality of our proposed method wasdemonstrated by an application in network pharmacology. Result : Network pharmacology results revealed that out of 196 compounds 22were actively interacting with known rheumatoid arthritis therapeutic targets andputative target genes. A multi-level network simulation identifies 33 majorcandidate targets including 8 compositive compounds, 10 therapeutic targets and15 putative target genes. The gene ontology and KEGG pathway enrichmenttarget validation demonstrated that candidate putative target genes were frequently involved in TNF, CCR5, IL-17 and G-protein coupled receptorssignaling pathways which are critical in the progression of rheumatoid arthritis.The molecular docking simulation and molecular descriptor analysis indicatedthat Glyceryl diacetate-2-Oleate, Hexadecanoic acid, 2,3-bis(acetyloxy)propylester, Glycidyl oleate, and Oleoyl chloride had a high binding affinity on theirmajor targets with their molecular descriptor properties indicating their potentialdrug likeliness for the treatment of rheumatoid arthritis. Conclusion : The findings of this study provides promising results that couldlead to design and discovery alternative drug compounds for management andtreatment of rheumatoid arthritis. Although our approach is purely based on insilico method, clinical experiments are still needed to test and validate thehypotheses of our computational methods.

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G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation

Cited by 12 publications

References 201 publications

Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis

Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis

Endothelin receptor B enhances liver injury and pro-inflammatory responses by increasing G-protein-coupled receptor kinase-2 expression in primary biliary cholangitis

An Efficient Weighted Network Centrality Approach for Exploring Mechanisms of Action of the RP-RB Herbal Formula for Treating Rheumatoid Arthritis

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