Cyclic AMP inhibits production of interleukin-6 and migration in human vascular smooth muscle cells

Walter H. Newman, Manuel R. Castresana, Jerry G. Webb, Zhongbiao Wang

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background. Gene expression induced by tumor necrosis factor-α (TNF-α) is involved in the regulation of vascular smooth muscle cell (VSMC) proliferation and migration, two events critical to formation of stenotic vascular lesions. In some systems, elevating adenosine 3′,5′-cyclic monophosphate (cyclic AMP) inhibits TNF-α induced gene transcription. We recently demonstrated that interleukin-6 (IL-6) was chemotactic to VSMC. Therefore, we tested the hypothesis that elevating cyclic AMP would inhibit TNF-α-mediated IL-6 expression and VSMC migration. Materials and methods. VSMC were cultured from saphenous vein remaining after coronary artery bypass grafting. Migration of VSMC through a porous membrane was determined. Intracellular cyclic AMP was elevated by exposing the cells to forskolin or 8-Br-cyclic AMP and was measured by radioimmunoassay. IL-6 was measured by enzyme-linked immunosorbent assay. Results. TNF-α induced migration of VSMC in a concentration-dependent manner. Incubation of cells with forskolin significantly increased cyclic AMP. Co-incubation of cells with TNF-α in combination with 8-Br-cyclic AMP or forskolin inhibited migration by approximately 25 and 70%, respectively. Incubation with TNF-α increased release of IL-6 from VSMC 18-fold over basal. This stimulated release was inhibited by either 8-Br-cyclic AMP or forskolin. In cells stimulated with TNF-α, addition of an antibody to IL-6 reduced migration by 25%. Conclusions. These data show that IL-6 produced by VSMC contributes to cell migration induced by TNF-α. Further, elevating cyclic AMP inhibited TNF-α-induced release of IL-6, and migration of VSMC. These results are consistent with the notion that mechanisms that increase intracellular cyclic AMP, such as activation of β-adrenergic receptors on VSMC, act as a brake on cell migration.

Original languageEnglish (US)
Pages (from-to)57-61
Number of pages5
JournalJournal of Surgical Research
Volume109
Issue number1
DOIs
StatePublished - Jan 2003
Externally publishedYes

Keywords

  • Cyclic AMP
  • Interleukin-6
  • Smooth muscle cell migration, tumor necrosis factor-α

ASJC Scopus subject areas

  • Surgery

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