Azithromycin treats diffuse panbronchiolitis by targeting T cells via inhibition of mTOR pathway.

Abstract

Azithromycin (AZM), that is a macrolide antibiotic, has been found to treat diffuse panbronchiolitis (DPB) effectively. However, the mechanism of action underlying the therapeutic effects remains unclear. We selected 64 patients with DPB from 305 patients who were diagnosed with DPB at the outpatient clinic in Shanghai Pulmonary Hospital from Jan 2010 to Oct 2014. The primary PBLs, CD4 + T cells, and Jurkat T cells were treated with AZM or erythromycin (EM), and the effects of AZM and EM on IL-17A and CXCL-2 production, proliferation, apoptosis and autophagy were evaluated. AZM and EM significantly inhibited IL-17A and CXCL-2 production in patients' PBLs (all P < 0.05). AZM significantly inhibited proliferation and promoted apoptosis of T cells from DPB patients. AZM can enhance autophagosome formation of T cells by suppressing S6RP phosphorylation, which is a downstream target of mTOR pathway (all P < 0.05). AZM and EM significantly decreased secreted IL-17A levels (P < 0.05) in the primary CD4 + T cells of patients with DPB. AZM may treat DPB patients by targeting cytokine production, proliferation, apoptosis and autophagy of T cell. The mechanism of therapeutic effects of AZM on DPB may be associated with a specific inhibition of mTOR pathway in the T lymphocytes.

• Authors: Dong Weng, Qin Wu, Xian-Qiu Chen, Yu-Kui Du, Tao Chen, Hong Li, Dan-Li Tang, Qiu-Hong Li, Yuan Zhang, Li-Qin Lu, Nian-Yu Zhou, Jia-Cui Song, Chen Wang, Hui-Ping Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 110 Pg. 440-448 (Feb 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 30530046 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Azithromycin
• MTOR protein, human
• TOR Serine-Threonine Kinases

Topics

• Adult
• Aged
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Azithromycin (pharmacology, therapeutic use)
• Bronchiolitis (drug therapy, metabolism)
• Dose-Response Relationship, Drug
• Female
• Haemophilus Infections (drug therapy, metabolism)
• Humans
• Jurkat Cells
• Male
• Middle Aged
• Signal Transduction (drug effects, physiology)
• T-Lymphocytes (drug effects, metabolism)
• TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)