Search

Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF- β 1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5′-adenosine monophosphate-activated protein kinase a (AMPK α) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p -AMPK α to AMPK α was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPK α activity and decreased asthma-related angiogenesis. [ABSTRACT FROM AUTHOR]

Asthma, airway inflammation, airway remodeling, metformin, AMPK Corrigendum: Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPK Activity Keywords: asthma; airway inflammation; airway remodeling; metformin; AMPK EN asthma airway inflammation airway remodeling metformin AMPK 1 1 1 04/26/22 20220421 NES 220421 In the published article, there was an error regarding the affiliation for "Changgui Wu". [Extracted from the article]

Objectives. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has immune- and inflammation-modulating properties in asthma, but its possible effects on asthmatic airway remodeling remain uncertain. In this study, we investigated the effects of 1,25-(OH)2D3 on airway remodeling in a murine model of chronic asthma and investigated its role in regulating nuclear factor- κB (NF- κB) activation. Methods. BALB/c mice were sensitized to ovalbumin (OVA) and subsequently exposed to intranasal OVA challenges for 9 weeks. Some mice also received an intraperitoneal injection of 1,25-(OH)2D3 at the time of challenge. At the end of the challenge period, mice were evaluated for chronic airway inflammation and airway remodeling. Nuclear translocation of NF- κB p65 in lung tissue was examined by Western blot. Inhibitor of NF- κB alpha (I κB α) expression was determined by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated I κB α protein expression was also determined by Western blot. Results. 1,25-(OH)2D3 treatment reduced OVA-induced chronic inflammation in lung tissue and attenuated established structural changes of the airways, including subepithelial collagen deposition, goblet cell hyperplasia, and increased airway smooth muscle mass. 1,25-(OH)2D3 also inhibited the nuclear translocation of NF- κB p65 in lung tissue. Concurrently, 1,25-(OH)2D3 induced increased I κB α protein levels via inducing increased I κB α mRNA levels and decreased I κBα phosphorylation. Conclusion. 1,25-(OH)2D3 could attenuate asthmatic airway remodeling and its inhibition of NF- κB activation may underlie this protective effect. [ABSTRACT FROM AUTHOR]