In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 23, No. 11 ( 2003-11), p. 2034-2040
Abstract:
Objective— Cyclosporin A (CsA) and tacrolimus (FK506) are widely used as immunosuppressants. However, their use has been hampered by various adverse effects, such as acceleration of atherosclerosis. Interleukin (IL)-8, a chemotactic cytokine, plays an important role in pathogenesis of atherosclerosis. We thus investigated whether synthesis of IL-8 from primary human aortic smooth muscle cells is influenced by CsA and FK506. Methods and Results— Northern blot analysis revealed that CsA increased IL-8 mRNA level and enhanced its increase by epidermal growth factor or tumor necrosis factor-α. In contrast, FK506 had no effect on the mRNA level. IL-8 accumulation in culture media was also increased by CsA. Stability of IL-8 mRNA was not affected by CsA, whereas luciferase reporter gene assay using the human IL-8 promoter revealed that CsA significantly augmented the promoter activity. Electrophoretic mobility shift assay showed that binding activity of activator protein (AP)-1 was increased by CsA, and introduction of a mutation into the AP-1 site in the promoter abolished its CsA-dependent activation. The increased AP-1 binding activity was accompanied by c-Fos synthesis. Conclusions— CsA stimulates synthesis of IL-8 via activation of AP-1 in human aortic smooth muscle cells, providing a novel aspect of biological effects of CsA on the cells.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.0000094234.60166.78
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
1494427-3
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