Sodium tanshinone IIA sulfonate inhibits cigarette smoke-induced airway inflammation via regulating cystic fibrosis transmembrane conductance regulator-mediated pathway (HUM1P.263)

Cystic fribrosis transmembrane conductance regulator (CFTR) is an important anti-inflammatory protein and confers to development of chronic obstructive pulmonary disease (COPD). Sodium tanshinone IIA sulfonate (STS) has been reported to be anti-inflammatory under various stimuli exposure, however, the underlying mechanisms were not fully understood. In this study, we found exposure to cigarette smoke (CS) led to COPD in mice, manifested by reduction in lung function, increases of inflammatory cell counts in bronchial alveolar lavage fluid , and alveoli enlargement; these changes were associated with reduced expression and chloride current of CFTR, greater activation of ERK1/2 and Nrf2, and greater levels of IL-6 and IL-8 in the lung. Treatment of STS aerosol (10mg·kg -1 ·day -1 ) attenuated these responses in COPD mice. In 16HBE human bronchial epithelial cells, exposure to CS extract resulted in reduced CFTR expression, activation of ERK1/2 and Nrf2, and increased IL-6 and IL-8 release; these were potentiated by rise of intracellular concentration of Cl - (70 mM), pretreatment with CFTR inhibitor inh-172 (10 mM) or Nrf2 activation, yet prevented by knockdown of Nrf2, inhibition of ERK1/2 activation, or STS (25uM) treatment. These results indicate that STS could inhibit CS-induced COPD development by preventing CS-induced CFTR reduction, thus inhibiting Cl - -ERK1/2-Nrf2 mediated pro-inflammatory cytokine production in airway epithelial cells.