Induction of intracellular ceramide by interleukin-1β in oligodendrocytes

Abstract

The sphingomyelin pathway has been implicated in mediating the effect of several extracellular agents leading to important biochemical and cellular changes. The aim of this investigation is to study interleukin-1 beta (IL-1 beta) signaling in oligodendrocytes. For this purpose, the CG4 oligodendrocyte cells were differentiated and incubated with IL-1 beta. This treatment induced a time- and dose-dependent increase of the endocellular ceramide. To mimic the effect of the elevation of endogenous ceramide, the CG4 cells were treated with the ceramide analogue C2-ceramide. Cell survival, measured with the MTT assay, showed that, by increasing the concentration of ceramide, up to 40% of CG4 cells were dying within 6 h, similar data were obtained with the primary differentiated oligodendrocytes. Condensation of chromatin, nuclear fragmentation, and formation of apoptotic bodies indicated that apoptosis was the cause of death. Surprisingly, long-term exposure (72 h) to increasing concentrations of IL-1 beta, which increases intracellular ceramide, did not induce oligodendroglial cell death. These results show that an increase of intracellular ceramide is not sufficient to induce apoptosis in oligodendrocytes and that IL-1 beta signaling through the ceramide pathway in these cells can mediate functions other than programmed cell death.

Expression of interleukin‐1 receptors and their role in interleukin‐1 actions in murine microglial cells

“…1). However, a high level of expression of IL-1RI has been reported in this cell type (Brogi et al 1997;Blasi et al 1999). Consequently, the low level of expression of IL-1RI in our microglial cell cultures may reflect expression of IL-1RI on O 2 A progenitor cells, but not on microglial cells.…”

“…Expression of IL-1RI, IL-1RII and IL-1RAcP has also been reported on astrocytes (Tomozawa et al 1995;Zetterstrom et al 1998;Pousset et al 2001) and oligodendrocytes (Brogi et al 1997;Blasi et al 1999).…”

Relationships of apoptotic signaling mediated by ceramide and TNF-α in U937 cells

“…8 In other studies, the generation of ceramide by interleukin-1b in dendrocytes was not associated with apoptosis, although exogenously added ceramide killed dendrocytes. 51 Furthermore, ceramide was not found to be an upstream messenger in the cell death signaling mediated by Fas. In these studies, ceramide generation was regarded as a consequence rather than a cause of apoptosis.…”

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

“…Interestingly, the ultrastructural characteristics that we have described in the present model resemble the ones observed in a model of demyelination using Theiler's virus. 40 IL-1 per se has been shown to be cytotoxic to adult oligodendrocytes in vitro, 14,15 while the treatment of rats subjected to experimental autoimmune encephalomyelitis (EAE) with IL-1ra, an endogenous antagonist of IL-1, resulted in delayed and milder disease. 41,42 Moreover, certain IL-1 polymorphisms and a high ratio of IL-1 over IL-1ra production have been associated with increased susceptibility to relapse-onset multiple sclerosis in families.…”

“…4,10,11 Moreover, blocking IL-1 action reduces neuronal loss and inflammation induced by experimental brain insults 9,12,13 and IL-1 has been shown to be cytotoxic for oligodendrocytes both in vitro and in vivo. 14,15 On the other hand, although most of the evidence points to a detrimental role of IL-1 in MS, it has been shown to promote repair of cuprizone-derived demyelination via IGF-1. 16 It has been shown that a single-bolus injection of IL-1 into the CNS parenchyma gives rise to delayed and localized neutrophil (PMN) recruitment, but no overt damage to CNS integrity.…”