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Azithromycin (AZM) is a broad-spectrum antibiotic widely used to treat infections. AZM has also been shown to have anti-inflammatory and immunomodulatory functions unrelated to its antibacterial activity which contribute to the effectiveness of this drug in chronic respiratory diseases. The mechanisms behind these beneficial effects are not yet fully elucidated. We have previously shown that AZM enhances barrier integrity of bronchial epithelial cells and directs them towards epidermal differentiation.
In this study, we analyzed the effect of AZM pre-treatment of bronchial and alveolar derived cell lines while mechanically stressed in a Cyclical Pressure Air-liquid interface Device (CPAD), that mimics the disruption of the epithelial barrier with increased inflammatory response in lung tissue, associated with ventilator-induced lung injury (VILI). Immunostainings along with imaging the cells in the electron microscope, show that barrier integrity of the epithelium is compromised by cyclically stressing the cells but maintained when cells were AZM pre-treated. Lamellar body formations were also revealed in AZM pre-treated cells possibly further supporting the barrier enhancing effects. RNA sequencing shows that the inflammatory response is attenuated by AZM pre-treatment before cyclical stress. Expression of YKL-40, an emerging inflammatory marker is shown to increase due to cyclical stress and by AZM treatment. These data suggest that AZM has barrier protective and immunomodulatory effects, attenuating the inflammatory response during mechanical stress and might therefore be lung protective during mechanical ventilation.
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