ArticleCells2019
GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Regulation of G protein-coupled receptor kinase 2 and its role in tumors.Journal of translational medicine · 2026Review
- Macrophage-centred crosstalk with infiltrating immune cells in rheumatoid arthritis and its regulation by mesenchymal stem cells.Journal of translational medicine · 2025Review
- The intersection of GRK2 and PGE2 in rheumatoid arthritis: a comprehensive update on pathophysiology and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- Efficacy of electro-acupuncture at "Weizhong" (BL40) on macrophage polarization in rats with injured lumbar multifidus.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics.Mediators of inflammation · 2025Review
- Lipoteichoic Acid Rescued Age-Related Bone Loss by Enhancing Neuroendocrine and Growth Hormone Secretion Through TLR2/COX2/PGE2 Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
- Saccharomyces cerevisiae β-glucan improves the response of trained macrophages to severe P. aeruginosa infections.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Alleviation of Rheumatoid Arthritis by Inducing IDO Expression withJournal of immunology research · 2024Article
- GRK2 inhibits Flt-1Acta pharmaceutica Sinica. B · 2024Article
- GRK2 Mediates Macrophage Polarization by Regulating EP4-cAMP-pCREB Signaling in Ulcerative Colitis and the Therapeutic Effect of Paroxetine on Mice with DSS-Induced Colitis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis.Pharmaceutical biology · 2022Article
- Early Gβγ-GRK2 Inhibition Ameliorates Osteoarthritis Development by Simultaneous Anti-Inflammatory and Chondroprotective Effects.International journal of molecular sciences · 2022Article
- The Neuroimmune Interplay in Joint Pain: The Role of Macrophages.Frontiers in immunology · 2022Review
- Inhibition of Histone H3 Lysine-27 Demethylase Activity Relieves Rheumatoid Arthritis SymptomsFrontiers in immunology · 2022Article
- Essential Fatty Acids and Their Metabolites in the Pathobiology of Inflammation and Its Resolution.Biomolecules · 2021Review
- Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis.Cells · 2021Review
- lncRNA-PACER upregulatesGastroenterology report · 2021Article
- Spermidine Inhibits Joints Inflammation and Macrophage Activation in Mice with Collagen-Induced Arthritis.Journal of inflammation research · 2021Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheumatoid arthritis (RA) is characterized by the massive infiltration of various chronic inflammatory cells in synovia. In synovial fluid of patients with RA, M1 macrophages are dominant among all subtypes of macrophages, the mechanisms of macrophages polarization imbalance in RA has not been fully illuminated. The prostaglandin E2 (PGE2) augments M2 polarization in part via the cyclic adenosine monophosphate (cAMP)-cyclic AMP responsive element binding (CREB) signaling. However, previous study found constant stimulus of PGE2 on fibroblast-like synovial cells of adjuvant arthritis rats induced the decrease of cAMP, which is primarily caused by G protein-coupled receptor kinase 2 (GRK2)-induced EP4 over- desensitization. Whether GRK2 mediated-EP4 over-desensitization reduces the level of cAMP and inhibits M2 polarization in RA is unclear. Here we observed M1 macrophages were dominant in peritoneal macrophages (PMs), bone-marrow-derived macrophages (BMMs) and synovial macrophages of collagen-induced arthritis (CIA) mice. PGE2 stimulated M2 polarization via the EP4-cAMP-CREB in normal mice, while failed to promote M2 polarization in the PMs of CIA mice. Further, we found the EP4 over-desensitization stimulated by PGE2 induced abnormal PGE2-cAMP-CREB signaling as well as the imbalance of macrophage polarization. Targeted disruption of GRK2 in Raw264.7 (RAW) through GRK2 siRNA or CRISPR/Cas9 downregulated the M1 macrophage markers, upregulated the M2 macrophage markers and the EP4 membrane localization. The reduced M1/M2 ratio and increased p-CREB expression were observed in BMMs and PMs of GRK2
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