Azithromycin induces apoptosis in airway smooth muscle cells through mitochondrial pathway in a rat asthma model

Liqin Wu; Juan Yin; Qi Zhang; Meiyan Wang; Wei Dai; Jian Zhou; Yuanrong Dai

doi:10.21037/atm-21-3478

Azithromycin induces apoptosis in airway smooth muscle cells through mitochondrial pathway in a rat asthma model

Ann Transl Med. 2021 Jul;9(14):1181. doi: 10.21037/atm-21-3478.

Authors

Liqin Wu¹, Juan Yin², Qi Zhang¹, Meiyan Wang¹, Wei Dai³, Jian Zhou⁴, Yuanrong Dai¹

Affiliations

¹ Department of Pulmonary Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Neurorehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Abstract

Background: The proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. Azithromycin (AZM) has been shown to decrease bronchial hyperresponsiveness and airway inflammation in asthmatics; however, the role of AZM in ASMC proliferation remains unclear. Thus, we investigated the effect of AZM on ASMC proliferation in a rat model of experimental asthma.

Methods: We isolated ASMCs from rats sensitized and challenged by ovabulmin (OVA), and then treated with different concentrations of AZM. Cytotoxicity of ASMC was evaluated by Cell Counting Kit-8 (CCK-8) assay, morphological change was examined with laser confocal microscope after Annexin V/propidium iodide (PI) double staining, mitochondrial membrane potential was determined with JC-1 staining, and the expression of cytochrome C was examined by western blot.

Results: The relative surface areas of airway wall and smooth muscle layers in OVA-sensitized rats were significantly increased compared to those in the control group. Furthermore, in OVA-sensitized rats, the mitochondrial membrane potential of ASMC was higher, while the expression of mitochondria cytochrome C was lower compared to that in control rats. After AZM treatment, ASMC apoptosis was increased, mitochondrial membrane potential reduced, and the protein level of cytosolic cytochrome C was increased.

Conclusions: This study demonstrated that AZM increased the apoptosis of ASMCs through a mitochondrial pathway, which might play an important role in ASMs proliferation during asthmatic remodeling.

Keywords: Azithromycin (AZM); airway smooth muscle cells (ASMCs); apoptosis; asthma; mitochondria.