Regulation of Tumor Necrosis Factor-Alpha Gene Expression in the Astrocyte
Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine with a diverse variety of biological functions on a wide range of cells (for review see Beutler and Cerami 1989; Vilcek and Lee 1991). TNF-α has especially been recognized as being one of the proinflammatory cytokines in a number of tissues, including the brain. Astrocytes, the most abundant glial cell in the brain, have been shown to be capable of producing many cytokines upon stimulation, including TNF-α (for review see Benveniste 1992). TNF-α is an important mediator of both inflammatory and immunological responses in the brain due to its interaction with astrocytes. TNF-α mediated responses include: 1) enhancement of ICAM-1 on human fetal astrocytes (Frohman et al. 1989); 2) enhancement of class II major histocompatibility complex (MHC) expression on astrocytes through its synergistic interaction with interferon-gamma (IFN-γ) or virus (Massa et al. 1987; Benveniste et al. 1989); 3) proliferation of adult astrocytes (Selmaj et al. 1990); and 4) induction of interleukin-6 (IL-6) production by astrocytes (Frei et al. 1989; Benveniste et al. 1990). Additionally, TNF-α may act as an autocrine regulator of astrocyte function as these cells both produce TNF-α (Robbins et al. 1987; Lieberman et al. 1989; Chung and Benveniste 1990) and express high affinity TNF-α receptors (Benveniste et al. 1989). TNF-α may also contribute to demyelination within the central nervous system (CNS) due to its ability to lyse oligodendrocytes, the myelin producing cell in the CNS (Robbins et al. 1987), and induce myelin damage (Selmaj and Raine 1988).
KeywordsExperimental Allergic Encephalomyelitis Human Fetal Astrocyte Tumor Necrosis Factor Gene Expression Human Astroglioma Cell
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