Fas/CD95 ligation induces proliferation of primary fetal astrocytes through a mechanism involving caspase 8-mediated ERK activation.

Background: Fas/CD95 is the best-studied member of the death receptor (DR) superfamily in the central nervous system where it can trigger cellular responses other than apoptosis, including the promotion of neurogenesis and neuritogenesis, stimulation of the progression of gliomas, and regulation of the immune response of astrocytes.

Methods: We have investigated the role of Fas/CD95 in the regulation of the proliferation of fetal astrocytes in vitro, as well as the signalling pathways involved.

Results: Fas/CD95 ligation stimulated the proliferation of primary fetal astrocytes, through a mechanism that depends on the activation of caspase 8 and subsequent phosphorylation of extracellular signal regulated kinase (ERK).

Bimodal effect of interferon-β on astrocyte proliferation and survival: Importance of nuclear factor-κB.

Accumulating evidence indicates that interferon-β (IFN-β) can modify the complex immunopathogenic scenario causing clinical relapse activity and disease progression in MS. However, the beneficial effects of IFN-β in MS patients may also depend on non-immune mechanisms, including the modulation of astrocyte function. In the present report, we have shown that, depending on the dose, IFN-β treatment can either promote astrocyte proliferation and survival, or result astrocyte death.

Resistance of neonatal primary astrocytes against Fas-induced apoptosis depends on silencing of caspase 8.

In the present report, we have found that primary fetal astrocytes express caspase 8 and undergo apoptosis in response to Fas ligation. In contrast, neonatal astrocytes do not express detectable levels of the enzyme and are resistant to Fas killing. Fas-induced apoptosis can be restored in these cells by up-regulation of caspase 8 expression by means of transient transfection with a caspase 8-encoding plasmid.

Interferon-beta protects astrocytes against tumour necrosis factor-induced apoptosis via activation of p38 mitogen-activated protein kinase.

Several large clinical trials have demonstrated that interferon-beta (IFN-beta) therapy is effective in the treatment of multiple sclerosis (MS) patients. However, the mechanisms underlying the beneficial effects of IFN-beta are not fully understood. Most of the effort in the study of the relevant mechanisms of IFN-beta has dealt with its immunomodulatory actions.

Mechanisms of interferon-beta-induced survival in fetal and neonatal primary astrocytes.

Background: We have previously shown that interferon-beta (IFN-beta) is a potent promoter of astrocyte survival. Although the mechanism(s) by which IFN-beta promotes astrocyte survival have not been completely elucidated, it has been shown that IFN-beta directly stimulates survival signaling pathways. In the present report, we took advantage of the differences in the susceptibility of fetal and neonatal astrocytes to apoptosis to further investigate the mechanism(s) underlying the antiapoptotic effect of IFN-beta.

Interferon beta promotes survival in primary astrocytes through phosphatidylinositol 3-kinase.

Although interferon-beta (IFN-beta) has been demonstrated to be effective in the treatment of multiple sclerosis (MS) patients, the mechanism(s) underlying its beneficial effects has not been uncovered yet. Until now, most of the effort in the study of the relevant mechanisms of IFN-beta has dealt with its ability to modulate the immune response. Only recently, it has been proposed that the beneficial effects of IFN-beta in MS patients could depend on its ability to modulate astrocyte function.