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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, but not IL-4, IL-5 or IL-13 induced angiogenesis in vitro. Top panel: representative light photomicrographs (4x original magnification) show formation of primitive vascular tubule structures by human vascular endothelial cells after 11 days of culture (top panel) with medium (A), VEGF (10 ng/mL) (B), IL-25 (10 ng/mL) (C), IL-4 (10 ng/mL) (D), IL-5 (10 ng/mL) (E) and IL-13 (10 ng/mL) (F). Bottom panel: computer-assisted quantification of total tubule lengths (G), numbers of branch points (H) and total numbers of tubules (I). Bars show the mean ± SEM of three separate experiments performed in duplicate. *p < 0.05. Mann–Whitney U test. *p < 0.05.
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Fig9: IL-25, but not IL-4, IL-5 or IL-13 induced angiogenesis in vitro. Top panel: representative light photomicrographs (4x original magnification) show formation of primitive vascular tubule structures by human vascular endothelial cells after 11 days of culture (top panel) with medium (A), VEGF (10 ng/mL) (B), IL-25 (10 ng/mL) (C), IL-4 (10 ng/mL) (D), IL-5 (10 ng/mL) (E) and IL-13 (10 ng/mL) (F). Bottom panel: computer-assisted quantification of total tubule lengths (G), numbers of branch points (H) and total numbers of tubules (I). Bars show the mean ± SEM of three separate experiments performed in duplicate. *p < 0.05. Mann–Whitney U test. *p < 0.05.

Mentions: In an in vitro angiogenesis assay, IL-25, but not IL-4, IL-5 or IL-13, induced lengthening and branching of microvascular tubules by HUVEC as compared with VEGF, which was used as a positive control (Figure 9).Figure 9


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, but not IL-4, IL-5 or IL-13 induced angiogenesis in vitro. Top panel: representative light photomicrographs (4x original magnification) show formation of primitive vascular tubule structures by human vascular endothelial cells after 11 days of culture (top panel) with medium (A), VEGF (10 ng/mL) (B), IL-25 (10 ng/mL) (C), IL-4 (10 ng/mL) (D), IL-5 (10 ng/mL) (E) and IL-13 (10 ng/mL) (F). Bottom panel: computer-assisted quantification of total tubule lengths (G), numbers of branch points (H) and total numbers of tubules (I). Bars show the mean ± SEM of three separate experiments performed in duplicate. *p < 0.05. Mann–Whitney U test. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig9: IL-25, but not IL-4, IL-5 or IL-13 induced angiogenesis in vitro. Top panel: representative light photomicrographs (4x original magnification) show formation of primitive vascular tubule structures by human vascular endothelial cells after 11 days of culture (top panel) with medium (A), VEGF (10 ng/mL) (B), IL-25 (10 ng/mL) (C), IL-4 (10 ng/mL) (D), IL-5 (10 ng/mL) (E) and IL-13 (10 ng/mL) (F). Bottom panel: computer-assisted quantification of total tubule lengths (G), numbers of branch points (H) and total numbers of tubules (I). Bars show the mean ± SEM of three separate experiments performed in duplicate. *p < 0.05. Mann–Whitney U test. *p < 0.05.
Mentions: In an in vitro angiogenesis assay, IL-25, but not IL-4, IL-5 or IL-13, induced lengthening and branching of microvascular tubules by HUVEC as compared with VEGF, which was used as a positive control (Figure 9).Figure 9

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