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

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.

Automated summary

Azithromycin can increase the apoptosis of airway smooth muscle cells through a mitochondrial pathway, which may play a key role in asthmatic remodeling.