Transforming growth factor-β1 is associated with inflammatory resolution via promoting M2c macrophage polarization in lung injury mice

Abstract

Abstract Macrophage polarization is vital for the resolution of inflammation and tissue injury. Here, we investigated the role of transforming growth factor (TGF)-β1 on macrophages polarization. In the mouse model of ventilation-induced lung injury, high tidal volume-induced injury and inflammation were resolved 3 days post-ventilation (PV3d) to PV10d, with increased elastic fiber, proteoglycan, and collagen, as well as higher TGF-β1 level. M1 increased temporarily, whereas M2a and M2c began to increase from PV3d. In vivo upregulating or neutralizing TGF-β1 expression indicated that an appropriate expression of TGF-β1 is required to resolve lung injury and inflammation via regulating macrophage polarization. M1 are the main pro-inflammatory macrophages to induce pulmonary edema and inflammation. Inhibition of M1 to M2a is associated with pulmonary injury and inflammation, but M2b is contributed to the attenuation of serum interleukin (IL)-1β and pulmonary IL-6 levels. M2c contributed to the attenuation of serum and pulmonary IL-6 levels as well as serum tumor necrosis factor-α levels. TGF-β1 is a crucial factor to promote M2b and M2c polarization with the reduction of pulmonary IL-6 levels. Together, secretion of TGF-β1-mediated macrophage polarization plays a crucial role in the resolution of inflammatory lung injury.