Interleukin-1ß induces differential gene expression in aortic smooth muscle cells*

R. R. Keen, K. D. Nolan, M. Cipollone, E. Scott, V. P. Shively, J. S T Yao, W. H. Pearce, H. P. Greisler

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Purpose: Abdominal aortic aneurysms are characterized by an accelerated turnover of extracellular matrix proteins and by an inflammatory infiltrate that releases the cytokines interleukin-1ß and tumor necrosis factor-α. We examined the gene expression of human aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells after treatment with interleukin-1ß and tumor necrosis factor-α by measuring the changes in smooth muscle cell collagen, elastin, collagenase, and tissue inhibitor of metalloproteinase messenger ribonucleic acid levels in response to these cytokines. Methods: Biopsy of aneurysmal aorta (n = 6) and donor normal aorta (n = 3) was obtained at operation. Medial smooth muscle cells were cultured, passaged (P2 to P4), and incubated with 0, 10, 100, or 1000 pg/ml interleukin-1ß, tumor necrosis factor-α, or platelet-derived growth factor for 24 hours. Total ribonucleic acid was harvested. Percentage changes in messenger ribonucleic acid from control levels for type I and type III procollagen, elastin, collagenase, 72 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by Northern hybridization. Analyses were performed with analysis of variance (p < 0.05). All comparisons between aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells represent comparisons between one aneurysmal aorta and one normal aorta. Results: Added interleukin-1ß resulted in significant, dose-dependent increases in the collagenase messenger ribonucleic acid level at all concentrations tested in both aneurysmal aorta and normal aorta. The increase in the collagenase messenger ribonucleic acid level ranged from a minimum increase of 123% for 10 pg/ml interleukin-1ß in aneurysmal aortic smooth muscle cells to a maximum of 450% for 1000 pg/ml interleukin-1ß in normal aortic smooth muscle cells. Interleukin-1ß caused a significant decrease in the steady-state messenger ribonucleic acid levels for type 1 procollagen in both aneurysmal and normal aorta. The greatest reduction in type 1 procollagen messenger ribonucleic acid levels occurred at 100 pg/ml interleukin-1ß in both aneurysmal aortic smooth muscle cells (–39%) and normal aortic smooth muscle cells (–48%). The only observed qualitative difference between aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells was the change in tissue inhibitor of metalloproteinase-1 messenger ribonucleic acid levels in response to added interleukin-1ß. In aneurysmal aortic smooth muscle cells interleukin-1ß at 1000 pg/ml significantly increased messenger ribonucleic acid levels by 82%, whereas levels of tissue inhibitor of metalloproteinase-1 messenger ribonucleic acid in normal aortic smooth muscle cells did not change in response to added interleukin-1ß. Interleukin-1ß did not alter messenger ribonucleic acid levels for type III procollagen, elastin, type IV collagenase, or tissue inhibitor of metalloproteinase-2 in aneurysmal aorta or normal aorta. When tumor necrosis factor-α or platelet-derived growth factor were added, this did not significantly change aneurysmal aortic smooth muscle cells messenger ribonucleic acid levels for collagenase, type IV collagenase, tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2, and type I and type III procollagen. Conclusions: These findings suggest that interleukin-1ß, through its effect on smooth muscle cell collagenase and collagen gene expression, mediates the increased matrix turnover observed in aneurysms. Macrophages may induce changes in aortic smooth muscle cell gene expression in a paracrine manner that could lead to aneurysm formation. (J VASC SURG 1994;20:774-86.)

Original languageEnglish (US)
Pages (from-to)774-786
Number of pages13
JournalJournal of Vascular Surgery
Volume20
Issue number5
DOIs
StatePublished - 1994

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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    Keen, R. R., Nolan, K. D., Cipollone, M., Scott, E., Shively, V. P., Yao, J. S. T., Pearce, W. H., & Greisler, H. P. (1994). Interleukin-1ß induces differential gene expression in aortic smooth muscle cells*. Journal of Vascular Surgery, 20(5), 774-786. https://doi.org/10.1016/S0741-5214(94)70165-2