| First Author | Isoda K | Year | 2010 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 30 |
| Issue | 4 | Pages | 708-15 |
| PubMed ID | 20110570 | Mgi Jnum | J:172146 |
| Mgi Id | MGI:5004759 | Doi | 10.1161/ATVBAHA.109.201749 |
| Citation | Isoda K, et al. (2010) Deficiency of interleukin-1 receptor antagonist induces aortic valve disease in BALB/c mice. Arterioscler Thromb Vasc Biol 30(4):708-15 |
| abstractText | OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra), one of the most important antiinflammatory cytokines, is crucial for homeostasis of the immune system. However, the role of IL-1Ra in aortic valve stenosis (AS) remains poorly understood [corrected]. METHODS AND RESULTS: IL-1Ra-deficient (IL-1Ra(-/-)) mice on the BALB/c background showed increased aortic valve leaflet thickness compared to wild-type mice at the age of 12 weeks (P<0.001). We used peripheral T-cell transplantation to examine the role of T cells in the development of AS. T cells from IL-1Ra(-/-) but not from wild-type mice induced increased aortic valve thickness in nu/nu mice. Moreover, IL-1Ra(-/-) T cells produced much higher levels of tumor necrosis factor (TNF)-alpha in culture supernatants after anti-CD3 antibody stimulation compared to wild-type mice (P<0.001). Finally, we studied the role of TNF-alpha in the development of AS in IL-1Ra(-/-) mice by generating double-gene-deficient (TNF-alpha(-/-)/IL-1Ra(-/-)) mice. Interestingly, TNF-alpha(-/-)/IL-1Ra(-/-) mice did not have AS. CONCLUSIONS: IL-1Ra deficiency in inflammatory cells induced aortic valve inflammation and TNF-alpha participates importantly in the development of AS in IL-1Ra(-/-) mice. |
