adenosine a2a receptor a2ar antagonist sch58261  (MedChemExpress)

Journal: Bioactive Materials

Article Title: Immunomodulatory supramolecular hydrogel for rheumatoid arthritis management via adenosine A2A receptor-mediated macrophage remodeling

doi: 10.1016/j.bioactmat.2025.11.031

Figure Lengend Snippet: The design of an inflammatory macrophages-targeted, acid-sensitive PNSH for delivery MTX and its role in promoting A2AR activation on M2 macrophages for arthritis therapy. (A)The structure of acid-sensitive polymer-nanomedicine supramolecular hydrogels, composed of drug-loaded MTX NPs. (B) Schematic illustration of arthritis therapy targeting inflammatory joint network via mPECN NPs-mediated release of MTX. This approach leverages MTX targeting the A2AR and repolarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Activation of A2AR and macrophage repolarization by mPECN-MTX NPs synergistically enhanced the anti-inflammatory effect of PNSH-mediated nanomedicine in an arthritis rat model.

Article Snippet: The selective adenosine A2A receptor (A2AR) antagonist SCH58261 (HY-19533) was purchased from MedChemExpress (Shanghai, China).

Techniques: Activation Assay, Polymer

Journal: Bioactive Materials

Article Title: Immunomodulatory supramolecular hydrogel for rheumatoid arthritis management via adenosine A2A receptor-mediated macrophage remodeling

doi: 10.1016/j.bioactmat.2025.11.031

Figure Lengend Snippet: MTX@PNSH promotes anti-inflammatory M2 macrophages through the A2AR signaling pathway. (A) The intracellular cAMP levels in Raw 264.7 cells were determined by homogeneous time-resolved fluorescence (HTRF) following different treatments. (B) qRT-PCR analysis of relative mRNA of A2ar with different treatments. (C) Immunostaining of A2AR expression in Raw 264.7 cells with different treatments. (D) Flow cytometry analysis of A2AR + cells in Raw 264.7 cells with different treatments and the percentage of A2AR + cells in Raw 264.7 cells with different treatments. (E) qRT-PCR analysis of relative mRNA expression of Pdl1 without LPS treatment. (F) qRT-PCR analysis of relative mRNA expression of Ido1 without LPS treatment. (G) qRT-PCR analysis of relative mRNA expression of Pdl1 with LPS treatment. (H) qRT-PCR analysis of relative mRNA expression of Ido1 with LPS treatments. (I) Western blotting analysis of A2AR protein level in macrophages after 24 h of different treatment with or without A2AR inhibitor. (J) Quantitative analysis of A2AR protein level in different treatments with or without A2AR inhibitor. (K) Flow cytometry analysis of CD11b and CD39 in Raw 264.7 cells with different treatments and the percentage of CD11b + CD39 + macrophages. (L) Flow cytometry analysis of CD11b and CD73 in Raw 264.7 cells with different treatments and the percentage of CD11b + CD73 + macrophages. (M) Flow cytometry analysis of CD11b and PD-L1 in Raw 264.7 cells after 24 h of different treatments and the percentage of CD11b + PD-L1 + macrophages in Raw 264.7 cells after 24 h of different treatments. Data are presented as mean ± SD, n = 3. Statistical significance was determined using one-way ANOVA, followed by Dunnett's post hoc test for comparisons between groups.

Article Snippet: The selective adenosine A2A receptor (A2AR) antagonist SCH58261 (HY-19533) was purchased from MedChemExpress (Shanghai, China).

Techniques: Fluorescence, Quantitative RT-PCR, Immunostaining, Expressing, Flow Cytometry, Western Blot

Journal: Signal Transduction and Targeted Therapy

Article Title: Inducible CD147 up-regulation boosts extended SARS-CoV-2 infection triggering severe COVID-19 independent of ACE2

doi: 10.1038/s41392-025-02551-x

Figure Lengend Snippet: SARS-CoV-2-induced CD147 expression is regulated by transcription factor AHR. a The expressions of CD147 and ACE2 in BEAS-2B cells were determined by western blot. b The expressions of CD147, AHR, AHRR, and CYP1A1 in BEAS-2B cells were determined by western blot with SARS-CoV-2 pseudovirus infection or RBD incubation. c The expression of CD147 was determined in BEAS-2B cells by western blot with the addition of AHR agonist 2 or AHR antagonist 5. d The relative luciferase signals in pseudovirus-infected BEAS-2B cells were determined by dual-luciferase reporter assays with the addition of AHR agonist 2 or AHR antagonist 5, *** p < 0.001. e The expression of CD147 in BEAS-2B-shCD147 cells and its control was determined by western blot. f The transfection efficiency of plasmid AHR was evaluated by western blot in BEAS-2B-shCD147 cells. g The relative luciferase signals were determined by dual-luciferase reporter assays in pseudovirus-infected BEAS-2B cells and BEAS-2B-shCD147 cells with or without the transfection of plasmid AHR, ns, not significant, *** p < 0.001. h The expression of CD147 was determined in AHR knockdown BEAS-2B cells by western blot. i The expression of CD147 was determined in pseudovirus-infected BEAS-2B cells by western blot with the addition of AHR antagonist 5. j Dual-luciferase reporter assays were performed after co-transfecting of the pGL3-Basic-CD147 promoter (−2000– − 1), pRL-TK, and plasmid AHR into HEK293T cells. The relative luciferase signal was detected using a Dual-Luciferase® Reporter Assay System, *** p < 0.001. k Nuclear and cytoplasmic protein extraction assays were performed to determine the nuclear expression and cytoplasmic expression of AHR in BEAS-2B cells with pseudovirus infection or RBD incubation. Lamin B1 and GAPDH were selected as controls for nuclear protein and cytoplasmic protein, respectively

Article Snippet: AHR agonist 2 (HY-144339, MCE) and AHR antagonist 5 (HY-141609, MCE) are potent agonist and inhibitor of AHR, respectively, which can regulate the transcription of AHR’s downstream genes by affecting its nuclear localization.

Techniques: Expressing, Western Blot, Infection, Incubation, Luciferase, Control, Transfection, Plasmid Preparation, Knockdown, Reporter Assay, Protein Extraction