Anti-inflammatory effect of Yu-Ping-Feng-SanviaTGF-β1 signaling suppression in rat model of COPD.
OBJECTIVE
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 1 (TGF-β1)/Smad2 signaling pathway and inflammatory cytokines, to clarify whether YPFS could attenuate inflammatory response dependent on TGF-β1/Smad2 signaling in COPD rats or cigarette smoke extract (CSE)-treated human bronchial epithelial (Beas-2B) cells.


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-β1/Smad2 signaling pathway. Furthermore, CSE-treated cells were employed to confirm whether the effect of YPFS was dependent on the TGF-β1/Smad2 signaling via knockdown Smad2 (Si-RNA), or pretreatment with the inhibitor of TGF-β1.


RESULTS
Administration of YPFS effectively alleviated injury of lung, suppressed releasing of pro-inflammatory cytokines and collagen deposition in COPD animals (P<0.05), whereas exogenous TGF-β1 promoted releasing of IL-1β, IL-6, TNFα (P<0.05). Administration YPFS reduced inflammatory response significantly, also down-regulated TGF-β1/Smad2 signalingin vivoandin vitro. Unexpectedly, knockdown Smad2 or inhibition of TGF-β1 abolished anti-inflammatory effect of YPFS in CSE-treated cells.


CONCLUSIONS
YPFS accomplished anti-inflammatory effects mainly by suppressing phosphorylation of Smad2, TGF-β1/Smad2 signaling pathway was required for YPFS-mediated anti-inflammation in COPD rats or CSE-treated Beas-2B cells.
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Zhong-Shan
ZS
Yang
Central laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan.
Jin-Yuan
JY
Yan
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Ni-Ping
NP
Han
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Wei
W
Zhou
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Yu
Y
Cheng
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Xiao-Mei
XM
Zhang
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Ning
N
Li
Faculty of Basic Medical Science, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan.
Jia-Li
JL
Yuan
COPD; Cytokine; Pro-inflammatory; TGF-β1/Smad2; YPFS