Induction of vascular cell adhesion molecule-1 expression by IL-4 in human aortic smooth muscle cells is not associated with increased nuclear NF-κB levels
✍ Scribed by Paul S. Wright; Judith R. Cooper; Keith E. Kropp; Steven J. Busch
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 244 KB
- Volume
- 180
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are upregulated in vascular endothelial and smooth muscle cells by cytokines produced at sites of inflammation. The cytokine profile for induction of VCAM-1, however, is different for the two cell types. Tumor necrosis factor-␣ (TNF-␣) induced both VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells (HUVECs; ED 50 ϳ 300 and 30 U/ml, respectively). TNF-␣ and interleukin-1 (IL-1) stimulated cell surface ICAM-1 expression, but not VCAM-1 expression, in human aortic smooth muscle cells (HASMCs). Conversely, IL-4 was a potent VCAM-1 inducer in HASMCs (ED 50 ϳ 100 pg/ml) but did not induce ICAM-1 expression. Nuclear extracts from IL-4-treated cells were compared with untreated cells for relative nuclear factor-kappa B (NF-B) levels by using an electrophoretic mobility shift assay and surface plasmon resonance techniques. No significant increase in nuclear NF-B DNA binding activity was detected in IL-4-treated HASMCs by either method of analysis. IL-1 and TNF-␣ stimulated nuclear NF-B levels by about fourfold and fivefold, respectively, in HASMCs. The antioxidant pyrrolidine dithiocarbamate (PDTC) similarly inhibited VCAM-1 upregulation in HASMCs incubated with IL-4 and in HUVECs incubated with TNF-␣ (IC 50 s of 25 and 40 M, respectively). These data suggest that a significant increase in nuclear NF-B levels is not necessary or sufficient for VCAM-1 upregulation in HASMCs and does not determine the relative sensitivity to inhibition of gene expression by PDTC.