The Nuclear Factor κ-B Signaling Pathway Participates in Dysregulation of Vascular Smooth Muscle Cells in Vitroand in Human Atherosclerosis*

In the lesions of atherosclerosis, vascular smooth muscle cells (SMC) display many functions characteristic of cytokine activation that likely contribute importantly to ongoing inflammation during human atherogenesis. The transcription factor nuclear factor κ-B (NFκB) often mediates the effects of cytokines on target cells, but the identity of Rel family members important in human SMC activation remains uncertain. In vitro, human SMC express multiple Rel family members. Of these, dimers of p65 and p50, but not a putative SMC-Rel, comprise basal and inducible NFκB binding activities. SMC express two inhibitor proteins IκBβ and IκBα. Interleukin-1β stimulation caused transient loss of IκBα and a sustained decrease of IκBβ that correlated with increased and persistent levels of p65/p50 protein and binding activity in the nucleus. SMC cultured under serum-free conditions displayed little NFκB activity, but addition of serum or platelet-derived growth factor did activate NFκB. In situ analyses showed no evidence for basal NFκB activity in SMC in vivo as nonatherosclerotic arteries did not contain nuclear p65 or p50 protein. However, the nuclei of intimal SMC within human atheroma did contain both Rel proteins. We conclude that (i) dimers of p65 and p50, but not SMC-Rel, comprise NFκB complexes in human SMC; (ii) stimulatory components in serum activate NFκB and likely account for previously reported “constitutive” NFκB activity in cultured SMC; and (iii) exposure to inflammatory cytokines may produce prolonged NFκB activation in SMC because of sustained decreases in the inhibitory subunit IκB-β.

• Publication year

  1997

• Venue

  Journal of Biological Chemistry

• Publication date

  1997-06-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.272.25.15817PMID 9188479
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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