Arsenic induces tumor necrosis factor alpha release and tumor necrosis factor receptor 1 signaling in T helper cell apoptosis.

Abstract

Long-term exposure to arsenic induces arsenical cancers in human beings. Arsenic has been shown to induce apoptosis in a variety of cell systems. Previous studies revealed that patients with arsenic-induced Bowen's disease showed a defective cell-mediated immunity and decreased percentages of T cell and T helper cell subpopulations in peripheral mononuclear cells. The purpose of this study was to investigate the effects of arsenic on T cell survival and function in mononuclear cells. Arsenic concentrations higher than 1 micro M induced tumor necrosis factor alpha release from mononuclear cells and caused a cytotoxic effect on T cells. When exposed to higher concentrations of arsenic, apoptosis was induced. CD4+ cells were the major apoptoic population in mononuclear cells. Tumor necrosis factor receptor 1 expression on CD4+ cells, but not Fas/FasL, was significantly enhanced by arsenic treatment compared to other mononuclear cells. Increased expressions of tumor necrosis factor receptor 1 related death domain proteins and activated caspases were observed. These findings indicate that tumor necrosis factor receptor 1 signaling is the major pathway in arsenic-induced T helper cell apoptosis.

• Authors: Hsin-Su Yu, Wei-Ting Liao, Kee-Lung Chang, Chia-Li Yu, Gwo-Shing Chen
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 119 Issue 4 Pg. 812-9 (Oct 2002) ISSN: 0022-202X [Print] United States
• PMID: 12406325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• Arsenic

Topics

• Adult
• Antigens, CD (analysis, physiology)
• Apoptosis (drug effects)
• Arsenic (toxicity)
• CD4-Positive T-Lymphocytes (drug effects, physiology)
• Humans
• Interferon-gamma (biosynthesis)
• Leukocytes, Mononuclear (drug effects, physiology)
• Receptors, Tumor Necrosis Factor (analysis, physiology)
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor-alpha (biosynthesis)