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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including those from the School of Psychological Sciences & Health - but also papers by researchers based within the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

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IKKalpha and IKKbeta function in TNFalpha-stimulated adhesion molecule expression in human aortic smooth muscle cells

MacKenzie, C. and Ritchie, E. and Paul, A. and Plevin, R.J. (2007) IKKalpha and IKKbeta function in TNFalpha-stimulated adhesion molecule expression in human aortic smooth muscle cells. Cellular Signalling, 19. pp. 75-80. ISSN 0898-6568

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Abstract

The role of NFκB and it's upstream kinases in regulating adhesion molecule expression in the smooth muscle of the vasculature remains controversial. We therefore examined the effect of blocking the NFκB pathway on TNFα-stimulated ICAM-1 and VCAM-1 expression in primary cultures of human aortic smooth muscle cells using an adenoviral wild-type IκBα construct (Ad.IκBα) and dominant-negative IKKα (Ad.IKKα+/−) and IKKβ (Ad.IKKβ+/−) constructs. Ad.IκBα treatment was found to block NFκB DNA-binding, and thereby completely prevent TNFα-stimulated ICAM-1 and VCAM-1 expression without influencing IKK activity. Ad.IKKβ+/− treatment completely inhibited TNFα-stimulated IKK kinase activity, IκBα degradation and NFκB DNA-binding in addition to completely blocking TNFα-stimulated ICAM-1 and VCAM-1 expression. Ad.IKKα+/− treatment however had no detectable effect on NFκB DNA-binding or ICAM-1 and VCAM-1 expression. Our results demonstrate that TNFα-stimulated ICAM-1 and VCAM-1 expression in human aortic smooth muscle cells is NFκB-dependent, that IKKβ is a suitable target for drug therapy and Ad.IKKβ+/− an effective inhibitor of TNFα-stimulated ICAM-1 and VCAM-1 expression.