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

Abstract

Abdominal aortic aneurysms are characterized by an accelerated turnover of extracellular matrix proteins and by an inflammatory infiltrate that releases the cytokines interleukin-l~ and tumor necrosis factor-m We examined the gene expression of human aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells after treatment with interleuldn-l~ and tumor necrosis factor-~ 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 ceils were cultured, passaged (P2 to P4), and incubated with 0, 10, 100, or 1000 pg/ml interleukin-l[~, tumor necrosis factor-~, 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-l~ 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-l~ in aneurysmal aortic smooth muscle cells to a maximum of 450% for 1000 pg/ml interleukin-l~ in normal aortic smooth muscle cells. Interleukin-ll3 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-1l~ 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 metailoproteinase-1 messenger ribonucleic acid levels in response to added interleukin-l~. In aneurysmal aortic smooth muscle cells interleukin-l~ 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-l~. Interleukin-l~ 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-~ o...

ATP stimulates MMP-2 release from human aortic smooth muscle cells via JNK signaling pathway

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Increased Secretion of Tissue Inhibitors of Metalloproteinases 1 and 2 From the Aortas of Cholesterol Fed Rabbits Partially Counterbalances Increased Metalloproteinase Activity

“…Because the secretion of TIMPs from normal isolated SMCs is constitutive, 11,13 recruitment of other cells including macrophages may explain the increased levels of TIMP secretion in atherosclerotic tissues. However, there is a report that TIMP-1 mRNA levels can be increased by inflammatory cytokines in SMCs derived from aortic aneurysms, 29 and hence, some of the increase might be the result of induction by cytokines.…”

Matrix Metalloproteinase-2 Production and Its Binding to the Matrix Are Increased in Abdominal Aortic Aneurysms

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