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IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model.

Yao X, Wang W, Li Y, Huang P, Zhang Q, Wang J, Wang W, Lv Z, An Y, Qin J, Corrigan CJ, Huang K, Sun Y, Ying S - Respir. Res. (2015)

Bottom Line: An in house assay was also utilised to compare the effects of IL-25 and other Th2-cytokines on angiogenesis by human vascular endothelial cells.Repetitive intranasal challenge with IL-25 alone or OVA alone in OVA-presensitised animals significantly increased peribronchial vWF (+) vessels in the murine airways, which was associated with remarkably elevated expression of amphiregulin, angiogenin, endothelin-1, bFGF, EGF, IGF-1, VEGF and ERG.The data suggest that chronic exposure of murine airways to IL-25 alone is able to reproduce a local angiogenic milieu.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China. yaoxiujuanhello@163.com.

ABSTRACT

Background: Th2-promoting cytokine IL-25 might contribute to bronchial mucosal vascular remodelling in asthma through its receptor expressed by vascular endothelial and vascular smooth muscle cells.

Methods: By utilising a newly established chronic asthma murine model induced by direct exposure of the airways to IL-25 alone, we examined effects of IL-25 on angiogenesis, vascular remodelling and expression of angiogenic factors, compared changes with those in a "classical" ovalbumin (OVA)-induced murine asthma model. IL-25 and OVA were intranasally instilled into the airways of BALB/c mice for up to 55 days. Airways vessels and angiogenic factors, including Von Willebrand Factor (vWF), amphiregulin, angiogenin, endothelin-1, transcription factor ERG, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF) in lung sections, homogenates and BAL fluid were detected and quantified by immunostaining or enzyme linked immunosorbent assay (ELISA). An in house assay was also utilised to compare the effects of IL-25 and other Th2-cytokines on angiogenesis by human vascular endothelial cells.

Results: Repetitive intranasal challenge with IL-25 alone or OVA alone in OVA-presensitised animals significantly increased peribronchial vWF (+) vessels in the murine airways, which was associated with remarkably elevated expression of amphiregulin, angiogenin, endothelin-1, bFGF, EGF, IGF-1, VEGF and ERG. IL-25, but not Th-2-cytokines induced human angiogenesis in vitro.

Conclusions: The data suggest that chronic exposure of murine airways to IL-25 alone is able to reproduce a local angiogenic milieu. Thus, blocking IL-25 may attenuate vascular remodelling and improve outcomes in asthma patients.

No MeSH data available.


Related in: MedlinePlus

IL-25 increased airways vWF expression. A: Representative photomicrographs of von Willebrand factor (vWF) immunoreactivity in lung sections from saline (NS)-, OVA- and IL-25-challenged mice at various time points as indicated (original magnification x20). B: Quantitative analysis of vWF+ blood vessels per unit area of lung sections. Data were collected from 3 independent experiments and are expressed as the mean ± SEM (n = 5 in each group of mice at each time point).*p < 0.05.
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Fig1: IL-25 increased airways vWF expression. A: Representative photomicrographs of von Willebrand factor (vWF) immunoreactivity in lung sections from saline (NS)-, OVA- and IL-25-challenged mice at various time points as indicated (original magnification x20). B: Quantitative analysis of vWF+ blood vessels per unit area of lung sections. Data were collected from 3 independent experiments and are expressed as the mean ± SEM (n = 5 in each group of mice at each time point).*p < 0.05.

Mentions: Immunoanalysis showed that IL-25, as compared with saline challenge induced marked airways angiogenesis as indicated by significantly elevated numbers of peri-bronchial, vWF+ immunoreactive blood vessels from day 36 and persisting until the end of the experiment (day 70) (Figure 1). Similarly, OVA challenged animals also showed elevated vWF+ immunoreactive vessels from days 36 to 55 which however declined by day 70 (Figure 1). Correspondingly, IL-25 challenge also significantly increased the expression of global airways ERG immununoreactivity from day 36 until day 70 (Figure 2). OVA challenge similarly increased ERG expression although this was evident slightly earlier from day 24 until the end of the experiment (Figure 2).Figure 1


IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model.

Yao X, Wang W, Li Y, Huang P, Zhang Q, Wang J, Wang W, Lv Z, An Y, Qin J, Corrigan CJ, Huang K, Sun Y, Ying S - Respir. Res. (2015)

IL-25 increased airways vWF expression. A: Representative photomicrographs of von Willebrand factor (vWF) immunoreactivity in lung sections from saline (NS)-, OVA- and IL-25-challenged mice at various time points as indicated (original magnification x20). B: Quantitative analysis of vWF+ blood vessels per unit area of lung sections. Data were collected from 3 independent experiments and are expressed as the mean ± SEM (n = 5 in each group of mice at each time point).*p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4390095&req=5

Fig1: IL-25 increased airways vWF expression. A: Representative photomicrographs of von Willebrand factor (vWF) immunoreactivity in lung sections from saline (NS)-, OVA- and IL-25-challenged mice at various time points as indicated (original magnification x20). B: Quantitative analysis of vWF+ blood vessels per unit area of lung sections. Data were collected from 3 independent experiments and are expressed as the mean ± SEM (n = 5 in each group of mice at each time point).*p < 0.05.
Mentions: Immunoanalysis showed that IL-25, as compared with saline challenge induced marked airways angiogenesis as indicated by significantly elevated numbers of peri-bronchial, vWF+ immunoreactive blood vessels from day 36 and persisting until the end of the experiment (day 70) (Figure 1). Similarly, OVA challenged animals also showed elevated vWF+ immunoreactive vessels from days 36 to 55 which however declined by day 70 (Figure 1). Correspondingly, IL-25 challenge also significantly increased the expression of global airways ERG immununoreactivity from day 36 until day 70 (Figure 2). OVA challenge similarly increased ERG expression although this was evident slightly earlier from day 24 until the end of the experiment (Figure 2).Figure 1

Bottom Line: An in house assay was also utilised to compare the effects of IL-25 and other Th2-cytokines on angiogenesis by human vascular endothelial cells.Repetitive intranasal challenge with IL-25 alone or OVA alone in OVA-presensitised animals significantly increased peribronchial vWF (+) vessels in the murine airways, which was associated with remarkably elevated expression of amphiregulin, angiogenin, endothelin-1, bFGF, EGF, IGF-1, VEGF and ERG.The data suggest that chronic exposure of murine airways to IL-25 alone is able to reproduce a local angiogenic milieu.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China. yaoxiujuanhello@163.com.

ABSTRACT

Background: Th2-promoting cytokine IL-25 might contribute to bronchial mucosal vascular remodelling in asthma through its receptor expressed by vascular endothelial and vascular smooth muscle cells.

Methods: By utilising a newly established chronic asthma murine model induced by direct exposure of the airways to IL-25 alone, we examined effects of IL-25 on angiogenesis, vascular remodelling and expression of angiogenic factors, compared changes with those in a "classical" ovalbumin (OVA)-induced murine asthma model. IL-25 and OVA were intranasally instilled into the airways of BALB/c mice for up to 55 days. Airways vessels and angiogenic factors, including Von Willebrand Factor (vWF), amphiregulin, angiogenin, endothelin-1, transcription factor ERG, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF) in lung sections, homogenates and BAL fluid were detected and quantified by immunostaining or enzyme linked immunosorbent assay (ELISA). An in house assay was also utilised to compare the effects of IL-25 and other Th2-cytokines on angiogenesis by human vascular endothelial cells.

Results: Repetitive intranasal challenge with IL-25 alone or OVA alone in OVA-presensitised animals significantly increased peribronchial vWF (+) vessels in the murine airways, which was associated with remarkably elevated expression of amphiregulin, angiogenin, endothelin-1, bFGF, EGF, IGF-1, VEGF and ERG. IL-25, but not Th-2-cytokines induced human angiogenesis in vitro.

Conclusions: The data suggest that chronic exposure of murine airways to IL-25 alone is able to reproduce a local angiogenic milieu. Thus, blocking IL-25 may attenuate vascular remodelling and improve outcomes in asthma patients.

No MeSH data available.


Related in: MedlinePlus