The receptor for tumor necrosis factor on murine astrocytes: Characterization, intracellular degradation, and regulation by cytokines and theiler's murine encephalomyelitis virus

Abstract

Previous reports have shown that tumor necrosis factor (TNF) exerts a role on the physiology of astrocytes under inflammatory situations. The signalling for biological effects of this and other cytokines are usually exerted through cell surface receptors. In this study, we have demonstrated the presence of a surface TNF alpha receptor type I in murine astrocytes of both SJL/J and BALB/c origin, using 125I-labelled recombinant mouse TNF alpha. A linear Scatchard plot indicates the presence of only one type of receptor with a MW of 58 kDa (Type I TNF receptor) that binds the ligand with a Kd of 1 x 10(-9) M. There are 3,000 copies of this receptor on untreated astrocytes. The results also indicate that receptor-bound TNF is rapidly internalized at 37 degrees C and degraded intracellularly to a principal molecular species which elutes from HPLC reverse-phase columns at 38% acetonitrile rather than at 60%, as native TNF alpha does. The binding is up-regulated by increasing the number of receptors (but not its affinity) by treatments with Theiler's murine encephalomyelitis virus (TMEV), Con A and inflammatory cytokines such as IL-1 alpha, IL-6, and INF-gamma. It is not influenced by vaccinia virus, IL-2, or LPS. This receptor may contribute to the initiation of perpetuation of the immune response which mediates the demyelinating inflammation induced by Theiler's virus.

Constitutive expression of p55TNFR mRNA and mitogen‐specific up‐regulation of TNFα and p75TNFR mRNA in mouse brain

“…Our evidence that oligodendrocytes might express p55TNFR conforms to observations demonstrating that p55TNFR is expressed in primary oligodendrocytes of man (Wilt et al, 1995). Furthermore, primary microglial cells (Wilt et al, 1995) and astrocytes (Aranguez et al, 1995) have been described to express the p55TNFR.…”

Biological risks for neurological abnormalities associated with hyperbilirubinemia

“…25 The early phase was detected as early as 15 min, peaking at 1 h, and the late phase occurred at 12 h. Although the early-phase activation may result from a direct interaction of UCB with the TNFR1, we speculate that the secondary activation may be attributed to the action of IL-1b and IL-6 produced during astrocyte exposure to UCB (Figure 1), which are known to upregulate TNFR1. 28 Downstream from the UCB-induced expression of TNFR1, a rapid and transient activation of p38 (1-2 h), JNK1/2 (1-4 h) and ERK1/2 (2 h) was observed, with nuclear translocation of NF-kB occurring from 1 h onward with a maximal localization in the nuclei of astrocytes of B12% at 4 h, 25 which was also observed for 100 mM UCB (unpublished data). To our knowledge, only the report of Lin et al 29 addresses this topic.…”

Long‐term modulation of glucose utilization by IL‐1α and TNF‐α in astrocytes: Na+ pump activity as a potential target via distinct signaling mechanisms

“…TNF-R55 and TNF-R75 represent the two types of TNF receptors that have been described; most of the signaling is normally associated with activation of TNF-R55 ( Vandenabeele et al, 1995). Moreover, expression of TNF receptors has been reported on astrocytes (Aranguez et al, 1995). Because the effect of TNF-␣ observed on glucose utilization is not prevented by IL-1ra, it is probably not secondary to stimulation of IL-1 expression, but rather is a direct consequence of TNF receptor activation.…”

“…IL-1 and TNF-␣ have pleiotropic effects in the central nervous system and are suspected to participate in functions as diverse as sleep, fever, and feeding behavior (Alheim and Bartfai, 1998;Krueger et al, 1998;Luheshi et al, 1999;Dantzer, 2001). Both IL-1 and TNF-␣ are formed within the brain and can act on astrocytes through independent receptors (Ban et al, 1993;Rubio, 1994;Aranguez et al, 1995). It was previously demonstrated that these two cytokines profoundly alter energy metabolism in astrocytes (Yu et al, 1995).…”