An IκB-α mutant inhibits cytokine gene expression and proliferation in human vascular smooth muscle cells

Zhongbiao Wang, Manuel R. Castresana, Kristina Detmer, Walter H. Newman

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background. Inflammatory reaction and intimal proliferation of smooth muscle cells are characteristics of vascular stenotic lesions. Nuclear factor κB (NF-κB) is involved in regulation of inflammation and cell survival in a variety of cell types. We tested a hypothesis that selective inhibition of NF-κB by expression of a mutated, nondegradable inhibitor of NF-κB, IκB-αM, would inhibit proinflammatory cytokine expression and proliferation in human vascular smooth muscle cell. Materials and methods. Smooth muscle cells were cultured from internal mammary artery and infected with recombinant adenovirus vectors. Results. Adenoviral expression of IκB-αM inhibited diverse signal-triggered cellular IκB-α degradation, subsequent NF-κB activation, and transactivation of proinflammatory cytokine genes. Expression of IκB-αM in low-density VSMC led to a 60% reduction in serum-stimulated cell growth and a 10% increment in apoptotic incidence but was without effect in high-density cultures. Coexpression of NF-κB p65 attenuated apoptosis in low-density cells induced by IκB-αM. Therefore, the susceptibility to apoptosis induction in the low-density cells correlated with lower constitutive NF-κB activity. The induction of apoptosis by IκB-αM and the rescue by NF-κB p65 might be explained by mutual control of NF-κB p65 and IκB-αM access to the nucleus. Conclusion. Our results suggest that expression of nondegradable IκB-α might have therapeutic potential in both vascular inflammatory reaction and smooth muscle cell proliferation.

Original languageEnglish (US)
Pages (from-to)198-206
Number of pages9
JournalJournal of Surgical Research
Volume102
Issue number2
DOIs
StatePublished - Jan 1 2002

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Vascular Smooth Muscle
Smooth Muscle Myocytes
Cytokines
Gene Expression
Apoptosis
Blood Vessels
Cell Count
Tunica Intima
Mammary Arteries
Adenoviridae
Transcriptional Activation
Cell Survival
Cell Proliferation
Inflammation
Incidence
Growth
Serum
Genes
Therapeutics

Keywords

  • Apoptosis
  • Cell growth
  • Cytokine gene expression
  • Nuclear factor-κB
  • Vascular smooth muscle cells
  • Viral-mediated gene transfer

ASJC Scopus subject areas

  • Surgery

Cite this

An IκB-α mutant inhibits cytokine gene expression and proliferation in human vascular smooth muscle cells. / Wang, Zhongbiao; Castresana, Manuel R.; Detmer, Kristina; Newman, Walter H.

In: Journal of Surgical Research, Vol. 102, No. 2, 01.01.2002, p. 198-206.

Research output: Contribution to journalArticle

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