Interleukin-25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL-17RB, but not IL-17RA
| Autor: | Wei Wang, Kewu Huang, Cailong Fang, Xiujuan Yao, Sun Ying, Tak H. Lee, Yunqing An, Christopher Corrigan, Qiu Meng, Y. Q. Fan, Z. Lv |
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| Rok vydání: | 2012 |
| Předmět: |
Angiogenesis
medicine.medical_treatment Immunology Basic fibroblast growth factor Neovascularization Physiologic Inflammation Biology chemistry.chemical_compound Interleukin 25 medicine Human Umbilical Vein Endothelial Cells Immunology and Allergy Humans Receptor Cells Cultured Receptors Interleukin-17 Interleukin-17 Endothelial Cells Molecular biology Endothelial stem cell Cytokine chemistry Gene Expression Regulation Cancer research Fibroblast Growth Factor 2 Interleukin 17 medicine.symptom Signal Transduction |
| Zdroj: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 42(11) |
| ISSN: | 1365-2222 |
| Popis: | SummaryBackground Unlike other IL-17 family members, the Th2-derived cytokine IL-25 (IL-17E) induces (promotes) Th2 responses. One or both of the two receptors for IL-25 (IL-17RA, IL-17RB) is expressed on inflammatory cells and tissue structural cells, suggesting that in addition to promoting Th2-type inflammation IL-25 may also act on structural cells at sites of Th2-type inflammation such as in the asthmatic bronchial mucosa to promote remodelling changes. Objective Our previous studies showed elevated expression of IL-25 and IL-17RB immunoreactivity in asthmatic airways with co-localization of the latter to endothelial cells. We therefore hypothesized that IL-25 acts on endothelial cells through this receptor to induce production of the key angiogenic and remodelling cytokine basic fibroblast growth factor (bFGF). Methods Polymerase chain reaction (PCR) immunocytochemistry/immunohistochemistry and ELISA were employed to detect expression of IL-17RB, IL-17RA and bFGF by human vascular endothelial cells (HUVEC) and immunoreactivity for IL-25 and bFGF in asthmatic bronchial biopsies. Receptor-blocking antibodies, PCR and an in vitro angiogenesis assay were used to investigate whether IL-25 acts on IL-17RB or IL-17RA to induce bFGF expression and angiogenesis. PCR was also employed to investigate the signalling pathways involved in IL-25-mediated bFGF expression. Results HUVEC constitutively expressed IL-17RB, IL-17RA and bFGF. Production of the latter was further increased by IL-25, but attenuated after blockade of the IL-17RB, but not the IL-17RA receptor. Neutralization of endogenous VEGF and bFGF completely abrogated IL-25-induced angiogenesis which was also inhibited by blocking IL-17RB, but not IL-17RA. The PI3K-specific inhibitor LY294002 also completely attenuated IL-25-induced bFGF expression. Immunoreactivity for IL-25 and bFGF was elevated in the asthmatic bronchial mucosa and the expression of each correlated with the other. Conclusions and Clinical Relevance Our data support the hypothesis that IL-25 contributes to elevated bFGF in asthmatic airways by acting on the endothelial cell IL-17RB receptor through PI3K-signalling pathways. Targeting the pathways might benefit therapy of airways remodelling. |
| Databáze: | OpenAIRE |
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