Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice.

Chamberlain, Janet, Evans, David, King, Andrea, Dewberry, Rachael, Dower, Steven, Crossman, DC and Francis, Sheila (2006) Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. American Journal of Pathology, 168 (4). pp. 1396-1403. ISSN 0002-9440

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Abstract

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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Rhiannon Harvey
Date Deposited: 17 May 2011 16:56
Last Modified: 02 Apr 2019 00:59
URI: https://ueaeprints.uea.ac.uk/id/eprint/30723
DOI:

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