Apoptosis of Vascular Smooth Muscle Cells Induced by In Vitro Stimulation With Interferon-γ, Tumor Necrosis Factor–α, and Interleukin-1β

Abstract

Recent studies have documented evidence for the death of smooth muscle cells (SMCs) within advanced human atheroma. These lesions contain macrophages and T lymphocytes in addition to SMCs. We therefore investigated whether interferon-γ (IFN-γ), a cytokine secreted by T lymphocytes, or interleukin-1β (IL-1β) and tumor necrosis factor–α (TNF-α), two cytokines characteristically produced by activated macrophages, can trigger apoptosis of vascular SMCs. Simultaneous treatment with IFN-γ and TNF-α and/or IL-1β but not with each cytokine alone promoted death of human and rat SMCs. Exposure for 48 hours to a combination of IFN-γ (400 U/mL), TNF-α (400 U/mL), and IL-1β (100 U/mL) significantly (P<.001) increased the accumulation of oligonucleosomes comprising DNA fragments and histones in human SMCs. Electrophoresis of genomic DNA showed internucleosomal fragments of genomic DNA isolated from the cytokine-cotreated SMCs of both humans and rats. These cells exhibited morphological changes typical of apopt...