Transforming growth factor-β1 is associated with inflammatory resolution via regulating macrophage polarization in lung injury model mice.

OBJECTIVE

Ventilation is the main respiratory support therapy for acute respiratory distress syndrome, which triggers acute lung injury (ALI). Macrophage polarization is vital for the resolution of inflammation and tissue injury. We hypothesized that transforming growth factor (TGF)-β1 may attenuate inflammation and ventilator-induced ALI by promoting M2 macrophage polarization.

METHODS

C57BL/6 mice received 4-hour ventilation and extubation to observe the resolution of lung injury and inflammation. Lung vascular permeability, inflammation, and histological changes in the lungs were evaluated by bronchoalveolar lavage analysis, enzyme linked immunosorbent assay, hematoxylin and eosin staining, as well as transmission electron microscope. TGF-β1 cellular production and macrophage subsets were analyzed by flow cytometry. The relative expressions of targeted proteins and genes were measured by immunofuorescence staining, Western blot, and quantitative polymerase chain reaction.

RESULTS

High tidal volume-induced injury and inflammation were resolved at 3 days of post-ventilation (PV3d) to PV10d, with increased elastic fibers, proteoglycans, and collagen content, as well as higher TGF-β1 levels. M1 macrophages were increased in the acute phase, whereas M2a macrophages began to increase from PV1d to PV3d, as well as increased M2c macrophages from PV3d to PV7d. A single dose of rTGF-β1 attenuated lung injury and inflammation at end of ventilation with polymorphonuclear leukocyte apoptosis, while nTAb pretreatment induced the abnormal elevation of TGF-β1 that aggravated lung injury and inflammation due to the significant inhibition of M1 macrophages polarized to M2a, M2b, and M2c macrophages.

CONCLUSIONS

Precise secretion of TGF-β1-mediated macrophage polarization plays a crucial role in the resolution of ventilator-induced inflammatory lung injury.