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

C. MacKenzie, E. Ritchie, A. Paul, R.J. Plevin

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

LanguageEnglish
Pages75-80
Number of pages6
JournalCellular Signalling
Volume19
DOIs
Publication statusPublished - 2007

Fingerprint

Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Smooth Muscle Myocytes
Tumor Necrosis Factor-alpha
DNA
Phosphotransferases
Smooth Muscle
Therapeutics
Drug Therapy

Keywords

  • human aortic smooth muscle cells
  • vascular cell adhesion molecule-1
  • intercellular adhesion molecule-1
  • nuclear factor kappa B
  • inhibitory kappa B kinase

Cite this

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title = "IKKalpha and IKKbeta function in TNFalpha-stimulated adhesion molecule expression in human aortic smooth muscle cells",
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.",
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IKKalpha and IKKbeta function in TNFalpha-stimulated adhesion molecule expression in human aortic smooth muscle cells. / MacKenzie, C.; Ritchie, E.; Paul, A.; Plevin, R.J.

In: Cellular Signalling, Vol. 19, 2007, p. 75-80.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Ritchie, E.

AU - Paul, A.

AU - Plevin, R.J.

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AB - 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.

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