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


Methods
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.


Results
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.


Conclusion
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.
['Hong|Liang-Jian|LJ|', 'Chen|Ai-Jun|AJ|', 'Li|Feng-Zeng|FZ|', 'Chen|Ke-Jun|KJ|', 'Fang|Sheng|S|']
D000818:Animals D016227:Benzoquinones D049109:Cell Proliferation D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D005260:Female D000071679:Glycogen Synthase Kinase 3 beta D018841:HSP90 Heat-Shock Proteins D047029:Lactams, Macrocyclic D051379:Mice D019463:Mice, Inbred MRL lpr D015394:Molecular Structure D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D013329:Structure-Activity Relationship D013601:T-Lymphocytes
HSP90 17-AAG activation AKT lupus