Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Biomed Pharmacother. 2019 Feb;110:440-448. doi: 10.1016/j.biopha.2018.11.090. Epub 2018 Dec 5.
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.
阿奇霉素（AZM）是一种大环内酯类抗生素，已被发现可有效治疗弥漫性泛细支气管炎（DPB）。然而，其治疗效果的作用机制仍不清楚。我们从 2010 年 1 月至 2014 年 10 月在上海肺科医院门诊诊断为 DPB 的 305 例患者中选择了 64 例 DPB 患者。用 AZM 或红霉素（EM）处理原发性 PBLs、CD4+T 细胞和 Jurkat T 细胞，评估 AZM 和 EM 对 IL-17A 和 CXCL-2 产生、增殖、凋亡和自噬的影响。AZM 和 EM 显著抑制患者 PBLs 中 IL-17A 和 CXCL-2 的产生（均 P<0.05）。AZM 显著抑制 DPB 患者 T 细胞的增殖并促进其凋亡。AZM 通过抑制 mTOR 通路的下游靶标 S6RP 磷酸化，增强 T 细胞的自噬体形成（均 P<0.05）。AZM 和 EM 显著降低了 DPB 患者原代 CD4+T 细胞分泌的 IL-17A 水平（P<0.05）。AZM 可能通过靶向 T 细胞的细胞因子产生、增殖、凋亡和自噬来治疗 DPB 患者。AZM 对 DPB 的治疗效果的机制可能与 T 淋巴细胞中 mTOR 通路的特异性抑制有关。
