| First Author | Chamberlain J | Year | 2006 |
| Journal | Am J Pathol | Volume | 168 |
| Issue | 4 | Pages | 1396-403 |
| PubMed ID | 16565512 | Mgi Jnum | J:107324 |
| Mgi Id | MGI:3620857 | Doi | 10.2353/ajpath.2006.051054 |
| Citation | Chamberlain J, et al. (2006) Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. Am J Pathol 168(4):1396-403 |
| abstractText | Interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Here, we examined the role of IL-1 in arterial neointima formation. Carotid artery neointima was induced by ligation, and arteries were harvested 4 weeks after injury. The neointima/media of mice deficient in the IL-1 signaling receptor (IL-1R1(-/-)) was significantly reduced compared to IL-1R1(+/+) controls (P < 0.01). IL-1R1(+/+) mice receiving subcutaneous IL-1ra also had significantly reduced neointima/media compared with placebo (P < 0.05). IL-1beta(-/-) mice had reduced neointima/media compared to wild-type (P < 0.05), whereas IL-1alpha(-/-) mice were no different from controls. Mice deficient in the P2X(7) receptor (involved in IL-1 release) or caspase-1 (involved in IL-1 activation) did not differ in their response to carotid ligation compared to controls. To examine the site of IL-1 signaling, we generated chimeric mice. IL-1R1(+/+) mice receiving IL-1R1(-/-) marrow and IL-1R1(-/-) mice receiving IL-1R1(+/+) marrow both had significantly reduced neointima/media compared with IL-1R1(+/+) to IL-1R1(+/+) (P < 0.05) but had significantly greater neointima/media than IL-1R1(-/-) to IL-1R1(-/-) controls (P < 0.05). These data confirm the importance of IL-1beta signaling in mediating arterial neointima formation and suggest the involvement of IL-1 signaling in both circulating and arterial wall cells. Furthermore, receptor antagonism may be a better therapeutic target than interruption of IL-1beta processing or release. |
