Induction by vasoactive intestinal peptide of interferon α/β synthesis in glial cells but not in neurons

Abstract

Vasoactive intestinal peptide (VIP), a 28-amino acid peptide, plays a multifunctional neuromodulatory role in both peripheral and central nervous systems. We have recently reported that VIP induces interferon (IFN) alpha/beta synthesis in human colon adenocarcinoma cell line HT-29. It has been reported that VIP may counteract HIV-induced neuronal cell death; therefore, we postulated that the action of VIP may be mediated by a cascade regulation, involving the production of some cytokines such as IFN. Here we demonstrate that primary cultures of rat mesencephalic neurons and glial cells respond differently to VIP. Thus VIP enhanced 2'5' oligoadenylate (2'5' A) synthetase activity and inhibited vesicular stomatitis virus multiplication in glial cultures only. However, both cell cultures had functional adenylate cyclase coupled receptors for VIP. The increase in 2'5'A synthetase activity in glial cultures reached a maximum with 10(-6) M VIP and required cellular RNA and protein synthesis. Anti-IFN alpha/beta, but not anti-IFN gamma, antibodies abolished the induction of the antiviral and 2'5'A synthetase activities by VIP in rat glial-enriched cultures, suggesting that these inductions were mediated through IFN alpha/beta synthesis. Moreover, VIP or poly (i). poly (C12U) caused, in the glial cultures, the induction and secretion of an IFN of type alpha/beta with a titer value of 16 and 32 units/ml respectively. In contrast, neither of these two substances was able to induce IFN synthesis in neurons, which were, however, sensitive to IFN alpha/beta produced by VIP-treated glial cells. IFN produced by VIP in glial cells may therefore play an important role in defending the brain against viruses.

Evaluation of the protective effect of oestradiol against toxicity induced by 6‐hydroxydopamine and 1‐methyl‐4‐phenylpyridinium ion (MPP+) towards dopaminergic mesencephalic neurones in primary culture

“…Culture plates were coated overnight at room temperature with poly d ‐lysine (10 µg/mL in 0.15 m sodium borate, pH 8.4), rinsed four times with water and incubated for 1 h at 37°C in basal medium supplemented with 20% fetal calf serum. These culture conditions led to neurone‐enriched cultures, astrocytes representing less than 1% of the total cell population after 7 days in vitro , as we previously observed following GFAP immunocytochemistry (Chelbi‐Alix et al . 1994).…”

“…Culture plates were coated for 10 min at room temperature with poly d ‐lysine (20 µg/mL H 2 O), rinsed twice with water and once with PBS. These culture conditions led to mixed neuronal–glial cultures, astrocytes representing around 20% of the total cell population after 7 days in vitro , as we previously observed by immunocytochemistry for glial fibrillary acidic protein (GFAP) (Chelbi‐Alix et al . 1994).…”

Localization of 2′,5′-oligoadenylate synthetase and the enhancement of its activity with recombinant interferon-α A/D in the mouse brain

“…Some reports indicate that IFNs are produced by neurons or glial cells in the brain (Tedeschi et al 1986;Olsson et al 1989;Ljungdahl et al 1989;Kiefer and Kreutzberg 1990;Chelbi-Alix et al 1994). Therefore, we suggestd that 42-kD 2-5AS activity would be predominantly localized to neurons and/or glial cells throughout the brain.…”

Vasoactive intestinal peptide: Mediator of laminin synthesis in cultured Schwann cells

“…This neuronal effect was subsequently shown to be due to VIP's mitogenic and neurotrophin-releasing actions on astrocytes (Brenneman et al, 1990). More recent reports of VIP effects on CNS glia include the induction of immediate early gene expression and process formation in cultured astrocytes (Hisanaga et al, 1993) and the upregulation of interferon a@ synthesis (Chelbi-Alix et al, 1994).…”