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

Chamberlain, Janet and Evans, David and King, Andrea and Dewberry, Rachael and Dower, Steven and Crossman, David 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-1β−/− mice had reduced neointima/media compared to wild-type (P < 0.05), whereas IL-1α−/− mice were no different from controls. Mice deficient in the P2X7 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-1β 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-1β processing or release.

Item Type: Journal Article
Journal or Publication Title: American Journal of Pathology
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2700/2734
Subjects:
Departments: Faculty of Health and Medicine
ID Code: 73544
Deposited By: ep_importer_pure
Deposited On: 18 Jun 2015 05:38
Refereed?: Yes
Published?: Published
Last Modified: 01 Jan 2020 09:11
URI: https://eprints.lancs.ac.uk/id/eprint/73544

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