Azithromycin treats diffuse panbronchiolitis by targeting T cells via inhibition of mTOR pathway - 06/01/19
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Graphical abstract |
Highlights |
• | Azithromycin inhibited proliferation of diffuse panbronchiolitis patients’ T cells. |
• | Azithromycin promoted apoptosis of diffuse panbronchiolitis patients’ T cells. |
• | Azithromycin can reduce IL-17 A in diffuse panbronchiolitis patients’ CD4 + T cells. |
• | Azithromycin can enhance autophagosome formation of T cells. |
• | Azithromycin inhibited mTOR pathway in diffuse panbronchiolitis patients’ T cells. |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Azithromycin, CD4+ T cells, Diffuse panbronchiolitis, IL-17A, mTOR
Plan
Vol 110
P. 440-448 - février 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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