Triptolide inhibits transforming growth factor-β1-induced proliferation and migration of rat airway smooth muscle cells by suppressing nuclear factor-κB but not extracellular signal-regulated kinase 1/2

Airway remodelling contributes to increased mortality in asthma. We have reported that triptolide can inhibit airway remodelling in a mouse asthma model. In this study, we aimed to investigate the effect of triptolide on proliferation and migration of airway smooth muscle cells (ASMC), and the possible mechanism. Rat ASMC were cultured and synchronized, then pre-treated with different concentrations of triptolide before being stimulated by transforming growth factor-beta(1) (TGF-beta(1)). Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of triptolide on the cell cycle. Migration was measured by Transwell analysis. Signal proteins [nuclear factor-kappa B (NF-kappa B) p65 and extracellular signal-regulated kinase 1/2 (ERK1/2)] were detected by Western blotting. A lactate dehydrogenase releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro-apoptotic effects of triptolide. Triptolide significantly inhibited TGF-beta(1)-induced ASMC proliferation and migration (P < 0.05). The cell cycle was dose-dependently blocked at G1/S-interphase by triptolide. Western blotting analysis showed that TGF-beta(1)-induced NF-kappa B p65 phosphorylation was inhibited by triptolide pre-treatment, but ERK1/2 was not affected. No cytotoxic or pro-apoptotic effects were detected under the concentration of triptolide that was used. Triptolide may function as an inhibitor of asthma airway remodelling by suppressing ASMC proliferation and migration through inactivation of the NF-kappa B pathway.