Experimental research The effects of budesonide on angiogenesis in a murine asthma model

Abstract

IntroductionThe aim of this study is to determine the effects and mechanisms of budesonide on angiogenesis in a murine asthma model.Material and methodsMurine asthma models were established and mice were divided into three groups: the model group (OVA-sensitized and challenged mice), the BUD group (budesonide-treated mice) and the PBS group (normal control mice). Mice in the BUD group were administered with inhaled budesonide (100 µg/kg) daily. The effects on airway inflammation, angiogenesis, expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were examined.ResultsAdministration of budesonide ameliorated allergic airway inflammation (2.90 ±0.18 vs. 4.80 ±0.20, p < 0.01) and significantly reduced the percentage vascularity (0.78 ±0.14 vs. 2.83 ±0.90, p < 0.01) compared with those in the asthmatic model mice. It also reduced the expression of HIF-1α (immunohistochemistry results: 71.70 ±1.40 vs. 89.60 ±0.79, p < 0.001; western blotting results: 0.88 ±0.41 vs. 0.97 ±0.47, p < 0.05), as well as that of VEGF (immunohistochemistry results: 26.30 ±1.03 vs. 93.30 ±1.54, p < 0.001; western blotting results: 1.12 ±0.22 vs. 2.08 ±0.30, p < 0.01). Percentage vascularity had positive correlation with both HIF-1α (r = 0.785, p < 0.01) and VEGF (r = 0.693, p < 0.01) expression. Furthermore, there is positive relationship between HIF-1α and VEGF expression (r = 0.641, p < 0.05).ConclusionsThe results demonstrate that budesonide has an important inhibitory effect on angiogenesis in asthma. Inhaled administration of budesonide achieved anti-angiogenic activity through inhibition of HIF-1α and VEGF expression. The results support a potential anti-remodeling role for budesonide in the treatment of human asthma.

Microvascular remodeling of nasal mucosa in allergic rhinitis induced by an allergen in Sprague-Dawley rats

“…Recent studies showed that there is a causal relationship between nasal mucosa remodeling in AR and VEGF; the latter inhibits the remodeling process by the regulating the mechanism of the receptor (Moon et al, 2012). Budesonide can inhibit angiogenesis in asthma by inhibiting the expression of HIF-1a and VEGF (Sun et al, 2013). Our present results show that the expression levels of VEGF increase in AR rats, but they decreased after treatment with FP for 12 weeks.…”

Cytokine profiling in exhaled breath condensate after exercise challenge in asthmatic children with post-exercise symptoms

“…Possibly, a study that did not include the use of controller medications would have been a better way to examine EBC. Repeatability of the described changes in EBC and their possible effect on airway remodeling should be verified [ 19 , 20 ]. Finally, pharmacological modulation of the inflammatory response to exercise should be assessed [ 21 ].…”

Administration of JTE013 abrogates experimental asthma by regulating proinflammatory cytokine production from bronchial epithelial cells

“…In this point, there are some limitations to interpret our in vivo data. Though extrapolating from our studies with intratrachial administration in mouse model to the allergic reaction in humans requires cautious interpretation, our data can provide significant promise to JTE013 as the remedy because previous study showed that asthma mouse model can be used to investigate the main point of our pathogenesis, allergic reaction through the cytokine production [48] and previous report showed the intratrachial administration of drugs such as budesonide in mice has similar efficacy in humans [49]. Therefore, I think our results can lead to the development of worthwhile therapeutic interventions.…”