Abstract
The study is to investigate the effect of cryptotanshinone (CTS) on airway remodeling and the possible mechanism. Male BALB/c mice were pretreated with CTS or dexamethasone 30 min before nebulized inhalation of ovalbumin (OVA). CTS significantly inhibited OVA-induced increases of eosinophils and neutrophils infiltration of bronchoalveolar lavage fluids (BALFs), reduced airway resistance in asthmatic mice, decreased the accumulation of inflammatory cells, the hyperplasia of goblet cells and the deposition of collagen in asthmatic mice lung tissue, as well as markedly attenuated the leakage of inflammatory cells and the level of OVA-specific immunoglobulin E in BALFs. CTS also inhibited the expressions of alpha-smooth muscle actin, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), Fn14, transforming growth factor (TGF)-β1, Smad4, and phosphorylation of Smad2/3 and STAT3 (Tyr705). In comparison to TWEAK inhibitor or TWEAK small interfering RNA (siRNA), which were used to inhibit TWEAK/STAT3 signaling pathways, CTS caused a similar effect as them on airway remodeling. Additionally, CTS also played a similar role as the TGF-β1 inhibitor or TGF-β1 siRNA in TGF-β1/STAT3 signaling pathways in airway remodeling. The anti-inflammatory effects of CTS against OVA-induced airway remodeling may be through inhibiting STAT3, which further suppresses TWEAK and TGF-β1 signaling cross talk in asthma. CTS may be a promising therapeutic reagent for asthma treatment.
Highlights
Airway hyperresponsiveness (AHR), inflammation, and remodeling are the major characteristics of asthma; among them, airway remodeling, which occurs at a very early stage of asthma in parallel with inflammation, has gained attention (Capra and Rovati, 2014)
The numbers of total cells, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluids (BALFs) were markedly reduced by high dose CTS or DEX treatment compared to the OVA group (P < 0.05)
The intensity of p-Smad2/3, Smad4, and p-STAT3 staining decreased in the transforming growth factor (TGF)-β1-induced airway smooth muscle cells (ASMCs) after being treated with CTS (Figure 5E). These results indicate that CTS might reduce the airway remodeling via Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/STAT3 and TGF-β1/STAT3 signaling pathways
Summary
Airway hyperresponsiveness (AHR), inflammation, and remodeling are the major characteristics of asthma; among them, airway remodeling, which occurs at a very early stage of asthma in parallel with inflammation, has gained attention (Capra and Rovati, 2014). The pathological changes in airway remodeling include epithelial damage, subepithelial fibrosis, mucus gland hyperplasia, increased smooth muscle mall, and vascular hyperplasia. Airway remodeling can induce excessive narrowing of the airway and cause irreversible airway obstruction, eventually, intractable asthma is developed. Studies have shown that airway remodeling can occur independent of inflammation or pulmonary function changes (Stenmark et al, 2015). Great efforts have been directed toward the management of airway remodeling; few strategies have been proven to be effective. There is an urgent need to develop new therapeutic options for airway remodeling in asthma (Liu et al, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
