Anti-inflammatory effect of Yu-Ping-Feng-San via TGF-β۱ signaling suppression in rat model of COPD

Objective(s): Yu-Ping-Feng-San (YPFS) is a classical traditional Chinese medicine that is widely used for treatment of the diseases in respiratory systems, including chronic obstructive pulmonary disease (COPD) recognized as chronic inflammatory disease. However, the molecular mechanism remains unclear. Here we detected the factors involved in transforming growth factor beta ۱ (TGF-β۱)/Smad۲ signaling pathway and inflammatory cytokines, to clarify whether YPFS could attenuate inflammatory response dependent on TGF-β۱/Smad۲ signaling in COPD rats or cigarette smoke extract (CSE)-treated human bronchial epithelial (Beas-۲B) cells.  Materials and Methods: The COPD rat model was established by exposure to cigarette smoke and intratracheal instillation of lipopolysaccharide, YPFS was administered to the animals. The efficacy of YPFS was evaluated by comparing the severity of pulmonary pathological damage, pro-inflammation cytokines, collagen related genes and the activation of TGF-β۱/Smad۲ signaling pathway. Furthermore, CSE-treated cells were employed to confirm whether the effect of YPFS was dependent on the TGF-β۱/Smad۲ signaling via knockdown Smad۲ (Si-RNA), or pretreatment with the inhibitor of TGF-β۱. Results: Administration of YPFS effectively alleviated injury of lung, suppressed releasing of pro-inflammatory cytokines and collagen deposition in COPD animals (P<۰.۰۵), whereas exogenous TGF-β۱ promoted releasing of IL-۱β, IL-۶, TNFα (P<۰.۰۵). Administration YPFS reduced inflammatory response significantly, also down-regulated TGF-β۱/Smad۲ signaling in vivo and in vitro. Unexpectedly, knockdown Smad۲ or inhibition of TGF-β۱ abolished anti-inflammatory effect of YPFS in CSE-treated cells. Conclusion: YPFS accomplished anti-inflammatory effects mainly by suppressing phosphorylation of Smad۲, TGF-β۱/Smad۲ signaling pathway was required for YPFS-mediated anti-inflammation in COPD rats or CSE-treated Beas-۲B cells.

Keywords:

COPD , Pro-inflammatory , Cytokine , TGF-β۱/Smad۲ , YPFS