Differential Oligodendroglial Expression of the Tumor Necrosis Factor Receptors In Vivo and In Vitro

Abstract

The cytokine tumor necrosis factor‐α (TNFα) has been proposed to play a key role in the degenerative processes observed in demyelinating diseases such as multiple sclerosis (MS). In the immune system the cellular responses to TNF are mediated by two different receptors: TNF‐RI, which is involved in cell death, and TNF‐RII, which has been shown to mediate cell proliferation. We investigated the oligodendroglial expression of TNF‐RI and ‐RII. In vivo, in normal adult rodent brain, oligodendrocytes express TNF‐RII but not TNF‐RI. However, after 3 days in culture, both types of receptors were expressed by mature oligodendrocytes, purified from 4‐week‐old rats, suggesting that expression of TNF‐RI was induced by either the isolation process or the culture conditions. This inducibility of TNF‐RI may explain the differences in oligodendrocyte cell death reported in various experimental conditions and in the pathology of MS lesions.

Insulin-Like Growth Factor (IGF) Signaling through Type 1 IGF Receptor Plays an Important Role in Remyelination

“…Cytotoxic factors, such as TNF-␣, that normally increase and then decrease with the cycle of demyelination and remyelination (Arnett et al, 2001) remain elevated within the middle region of the demyelinating lesion in ⌬Igf1r mice, most likely because of the continued presence of macrophages and some astrocytes (Arnett et al, 2001). TNF-␣ appears to have two opposite effects on oligodendrocytes and their progenitors, each mediated by a distinct TNF receptor (TNFR), both of which are upregulated during inflammatory conditions (Tchelingerian et al, 1995;Dopp et al, 1997). TNF-␣ produces cell death through TNFR1 (Haridas et al, 1998;Weiss et al, 1998;Ashkenazi and Dixit, 1999), but it also induces the proliferation of oligodendrocyte progenitors through TNFR2 (Arnett et al, 2001).…”

Cytokines and effector T cell subsets causing autoimmune CNS disease

“…TNF receptor 2 (TNFR2, p75) is preferentially activated by the transmembrane form of TNF [122,123] and is expressed by cells of the immune system including microglia but also by macroglial cells. Oligodendrocytes express TNFR2 in a constitutive manner and are induced to express TNFR1 by inflammatory stimuli [124]. While TNFR1 confers cytotoxic effects and promotes apoptosis, TNFR2 mediated signaling modulates apoptosis but can also result in cell growth and proliferation [125].…”

Post-Myocardial Infarction Depression

“…Cytokine receptors are present in different structures of the limbic system. For example, IL-1 receptors are found in the hypothalamus and the hippocampus; IL-6 receptors are located in the hippocampus, hypothalamus, the dentate gyrus and piriform cortex (Vitkovic et al 2000); TNF receptors are located in the hippocampus, cortex, amygdala, the basal ganglia (Vitkovic et al 2000) and are also expressed by oligodendrocytes (Tchelingerian et al 1995).…”