The HSP90 Inhibitor, 17-AAG, Influences the Activation and Proliferation of T Lymphocytes via AKT/GSK3β Signaling in MRL/lpr Mice

• Published in: Drug design, development and therapy Vol. 14; pp. 4605 - 4612
• Main Authors: Hong, Liang-Jian, Chen, Ai-Jun, Li, Feng-Zeng, Chen, Ke-Jun, Fang, Sheng
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2020; Dove; Dove Medical Press
• Subjects: 1-Phosphatidylinositol 3-kinase; 17-aag; activation; akt; AKT protein; Animals; Antibodies; Beads; Benzoquinones - chemistry; Benzoquinones - pharmacology; Cell activation; Cell culture; Cell cycle; Cell Proliferation - drug effects; Chronic conditions; Deposition; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flow cytometry; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta - metabolism; Heat shock proteins; Histopathology; hsp90; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Inhibitors; Kidneys; Laboratory animals; Lactams, Macrocyclic - chemistry; Lactams, Macrocyclic - pharmacology; Lupus; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred MRL lpr; Molecular Structure; Original Research; Proteins; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Signal Transduction - drug effects; Signaling; Stains & staining; Statistical analysis; Structure-Activity Relationship; Systemic lupus erythematosus; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Western blotting; HSP90; 17-AAG; AKT; activation; lupus
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S269725

To explore the molecular mechanism of 17-AAG in the treatment of systemic lupus erythematosus (SLE), and the effects of the heat shock protein 90 (HSP90) inhibitor 17-AAG on the activation and proliferation of lymphocytes and the AKT/GSK3β signaling pathway in MRL/lpr mice were detected. MRL/lpr mice were randomly divided into the control group and the experimental group. The experimental group was injected intraperitoneally with 17-AAG, and T lymphocytes were separated by magnetic beads. Lymphocyte proliferation was detected by MTT and flow cytometry (FCM), and the expression of the HSP90 protein and PI3K/AKT signaling pathway-related proteins was detected by Western blotting. Renal histopathology and immune complex deposition were also observed in both groups. Immune complex deposition and inflammation decreased in kidneys from MRL/lpr mice in the experimental group. HSP90 protein expression, T lymphocyte proliferation and phosphorylated AKT and GSK3β levels also decreased in the experimental group. 17-AAG can inhibit the activation and proliferation of T lymphocytes and downregulate the AKT/GSK3β signaling pathway, which may be relevant for the treatment of SLE.