Tracheal stenosis following injury cannot be effectively treated. The current study compared the protective effects of different anti-inflammatory drugs on tracheal stenosis and investigated their possible mechanisms. rabbit tracheal stenosis models following injury were constructed and confirmed using hematoxylin and eosin (H&E) staining. A total of 30 rabbits were divided into the control (CON), penicillin (PEN), erythromycin (ERY), budesonide (BUD) and PEN + ERY + BUD groups (n=6). Stenotic tracheal tissue, serum and bronchoalveolar lavage fluid (BALF) were collected 10 days after continuous treatment. Pathological changes in the tracheas were observed by H&E staining. Histone deacetylase 2 (HDAC2) expression in tracheal tissues was detected by immunofluorescence. Immunohistochemistry was performed to detect collagen I (Col-I) and collagen III (Col-III) levels in tracheal tissues. Transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) levels in serum and BALF samples were determined using ELISA kits. Western blotting detected HDAC2, IL-8, TGF-β1 and VEGF levels in tracheal tissues. H&E staining demonstrated that tracheal epithelial hyperplasia and fibroblast proliferation in the ERY and PEN + ERY + BUD groups markedly improved compared with the CON group. Furthermore, in tracheal tissues, HDAC2 expression was significantly increased and IL-8, TGF-β1, VEGF, Col-I and Col-III levels were significantly decreased in the ERY and PEN + ERY + BUD groups compared with the con group. additionally, the results for the PEN + ERY + BUD were more significant compared with the ERY group. In serum and BALF samples, IL-8, TGF-β1 and VEGF levels in the ERY and PEN + ERY + BUD groups were significantly lower compared with the CON group, with the results of the PEN + ERY + BUD group being more significant compared with the ERY group. There were no significant differences between the PEN, BUD and CON groups. ERY inhibited tracheal granulation tissue proliferation and improved tracheal stenosis following injury and synergistic effects with PEN and BUD further enhanced these protective effects. The mechanism may involve HDAC2 upregulation and inhibition of local airway and systemic inflammatory responses.
Objective. This study aims to explore the role of erythromycin-regulated histone deacetylase-2 in benign tracheal stenosis. Methods. The rabbit model of tracheal stenosis was established. The rabbits were randomly divided into 8 groups. Histone deacetylase-2 (HDAC2) expression was detected by immunofluorescence. The expression of type I collagen and type III collagen was detected by immunohistochemical method. The expression of TGF-β1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-β1, VEGF and IL-8 in bronchi of each group was detected by Western blotting method. Results. In Erythromycin (ERY) group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group, the degree of bronchial stenosis was alleviated, and the mucosal epithelium was still slightly proliferated. The effect of ERY combined with other drugs was more obvious. The HDAC2 protein expression increased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group and decreased significantly in Vorinostat group, the expression of collagen I and III decreased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group (P<0.05). The TGF-β1, IL-8 and VEGF levels decreased significantly in ERY group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group (P<0.05). Conclusions. Erythromycin inhibited inflammation and excessive proliferation of granulation tissue after tracheobronchial mucosal injury by up-regulating the expression of HDAC2, it promoted wound healing and alleviated tracheobronchial stenosis. When combined with budesonide, penicillin and other glucocorticoids and antibiotics, it had a good synergistic effect. However, vorinostat could attenuate erythromycin’s effect by down-regulating the expression of HDAC2. It may have good clinical application prospects in the treatment of tracheal stenosis.
The current treatments for benign tracheal stenosis are inefficient. The present study examined the expression of histone deacetylase 2 (HDAC2) in different tracheal stenosis models and explored its association with the proliferation of tracheal granulation tissue and its ability to constitute a potential therapy for tracheal stenosis. Animal tracheal stenosis models were established, as indicated by hematoxylin and eosin (H&E) staining. A total of 24 New Zealand White rabbits were randomly divided into control, erythromycin, budesonide and vorinostat groups. Stenotic tracheal tissues were collected on day 11 after drug administration for 10 days. The degree of tracheal stenosis in each group was calculated, and pathological alterations were observed using H&E staining. The mRNA expression of HDAC2, interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) was examined via reverse transcription-quantitative PCR. The protein expression of HDAC2 was examined via immunofluorescence, while the expression of type I and type III collagen was assessed using immunohistochemistry. The results of the present study demonstrated that tracheal epithelial hyperplasia in the erythromycin group was improved, the degree of hyperplasia being the lowest among all groups, and tracheal stenosis was reduced compared with the control group. In the vorinostat group, tracheal epithelial tissue hyperplasia was aggravated and stenosis was increased. The HDAC2 mRNA and protein levels were increased and decreased in the erythromycin and vorinostat groups, respectively. In contrast, the IL-8 mRNA expression levels were decreased and increased in the erythromycin and vorinostat groups, respectively. TGF-β1, VEGF, type I and type III collagen expression was decreased in the erythromycin group, while TGF-β1, VEGF and type III collagen expression was increased in the vorinostat group. Compared with the control, the budesonide group did not exhibit any alterations in all of the indicators examined, including TGF-β1, VEGF, IL-8, HDAC2 and collagen. Erythromycin treatment upregulated the expression of HDAC2, inhibited the inflammatory responses and reduced the proliferation of tracheal granulation tissue. In contrast, vorinostat treatment downregulated HDAC2 expression, promoted the inflammatory responses and increased the proliferation of tracheal granulation tissue. These results suggest that regulating HDAC2 may be used as a potential treatment for benign tracheal stenosis.
Bronchial asthma (abbreviated as asthma), is a heterogeneous disease characterized by chronic airway inflammation and airway hyperresponsiveness. The main characteristics of asthma include variable reversible airflow limitation and airway remodeling. The pathogenesis of asthma is still unclear. Th1/Th2 imbalance, Th1 deficiency and Th2 hyperfunction are classic pathophysiological mechanisms of asthma. Some studies have shown that the imbalance of the Th1/Th2 cellular immune model and Th17/Treg imbalance play a key role in the occurrence and development of asthma; however, these imbalances do not fully explain the disease. In recent years, studies have shown that γδT and γδT17 cells are involved in the pathogenesis of asthma. γδTreg has a potential immunosuppressive function, but its regulatory mechanisms have not been fully elucidated. In this paper, we reviewed the role of γδT17/γδTreg cells in bronchial asthma, including the mechanisms of their development and activation. Here we propose that γδT17/Treg cell subsets contribute to the occurrence and development of asthma, constituting a novel potential target for asthma treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.