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

Autor:	Hong LJ; Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China., Chen AJ; Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China., Li FZ; Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China., Chen KJ; Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China., Fang S; Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
Jazyk:	angličtina
Zdroj:	Drug design, development and therapy [Drug Des Devel Ther] 2020 Oct 29; Vol. 14, pp. 4605-4612. Date of Electronic Publication: 2020 Oct 29 (Print Publication: 2020).
DOI:	10.2147/DDDT.S269725
Abstrakt:	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. Competing Interests: The authors declare no conflicts of interest in this work. (© 2020 Hong et al.)
Databáze:	MEDLINE
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