4, P < 0·05). Triptolide and dexamethasone were equally effective in reducing levels of BALF TGF-β1 (512 ± 54 MK-8669 versus 524 ± 67 pg/ml, Fig. 4, P > 0·05). There was no significant difference between the TRP and DEX groups. We demonstrated that triptolide inhibited airway remodelling and reduced TGF-β1 expression. Recent reports have demonstrated an improved method for investigating the expression of active TGF-β1 signalling in situ,25 which involves examination of the expression of the intracellular effectors, Smads. Therefore, we investigated the expression patterns of phosphor-Smad2/3 (pSmad2/3) and Smad7 in the lung specimens following administration

of dexamethasone to investigate any effect on active TGF-β signalling in airway lesions. Data were normalized to the levels of GAPDH. An increase AZD3965 datasheet in expression of pSmad2/3 was observed during prolonged allergen challenge, whereas administration of triptolide and dexamethasone both considerably decreased pSmad2/3 expression (0·73 ± 0·07 versus 0·55 ± 0·04 and 0·51 ± 0·07, Fig. 5, Table 2, P < 0·01). In contrast with pSmad2/3, Smad7 was markedly up-regulated in mice treated with triptolide or dexamethasone compared with the OVA-sensitized/challenged group (0·44 ± 0·03 and 0·44 ± 0·04 versus 0·29 ± 0·06, Fig. 5, Table 2, P < 0·01). There was no significant difference of pSmad2/3 and Smad7 in mice treated with triptolide

and dexamethasone (Fig. 5, Table 2, P > 0·05).

In this study, we NADPH-cytochrome-c2 reductase established a mouse model of airway remodelling by repetitive OVA-challenge which replicated many of the features of the human disease asthma with a high degree of fidelity. Therefore, we investigated whether administration of triptolide could inhibit the progress of airway remodelling in mice exposed to repetitive allergen challenge, as well as determining whether triptolide could modulate the expression of signalling molecules of the TGF-β1/Smad pathway, which may in turn modulate airway remodelling. Recent morphological examination of airway tissues with bronchial asthma has revealed that abnormalities in airways, including goblet cell hyperplasia, mucous gland hypertrophy, subepithelial fibrosis and smooth muscle cell hyperplasia or hypertrophy, are in part irreversible.2,3 It is generally accepted that tissue remodelling is a process of wound healing for the maintenance of homeostasis after various injuries. Normally the process means the repair of injured tissues both morphologically and functionally; however, prolonged inflammation may induce remodelling of airways which could differ from wound healing. True to the observed clinical and symptomatic variability, remodelling can be elevated by as much as 50–300% in asthma patients who have died, and from 10 to 100% in subjects who have milder cases.26 Triptolide may offer a much needed therapeutic strategy for asthma airway remodelling.