Interleukin-1 alpha and vasoactive interstinal peptide: Enigmatic regulation of neuronal survival

D. E. Brenneman, J. M. Hill, G. W. Glazner, I. Gozes, T. W. Phillips

Research output: Contribution to journalArticlepeer-review

Abstract

A neurotrophic role for interleukin-1 alpha (IL-1α) was investigated in dissociated spinal cord-dorsal root ganglion cultures. Three observations suggested a survival-promoting action for IL-1α in nine-day-old cultures: (1) neutralizing antiserum to murine IL-1α decreased neuronal survival; (2) treatment with IL-1α in electrically blocked cultures increased neuronal survival; and (3) antiserum to the type I IL-1 receptor decreased neuronal survival. Treatment with VIP prevented neuronal cell death associated with the antiserum to IL-1α. In contrast, treatment of one-month-old cultures with IL-1α produced neuronal cell death and neutralizing antiserum to the IL-1 receptor had no effect on neuronal survival in these cultures. These experiments suggested that an IL-1-like substance was necessary for neuronal survival during a specific stage in development and that a relationship between VIP and IL-1α might account in part for the neurotrophic properties of VIP. To test if VIP might be a secretagogue for IL-1, a neuron-free model system was utilized: astroglial cultures derived from cerebral cortex. VIP treatment produced a concentration-dependent (EC50:50 pM) increase in the amount of IL-1α in the medium and a decrease in cellular IL-1α. Interleukin-1 beta (IL-1β) was also increased (EC 50: 1 nM) in the medium by VIP but without depleting IL-1β in the cytosol. Semi-quantitative measurements of the IL-1α mRNA after VIP treatment indicated a significant but transient decrease. These data indicate that VIP produced an increase in the secretion of IL-1α while depleting IL-1α mRNA.

Original languageEnglish
Pages (from-to)187-200
Number of pages14
JournalInternational Journal of Developmental Neuroscience
Volume13
Issue number3-4
DOIs
StatePublished - 1995

Keywords

  • VIP-IL-1 relationship
  • interleukin-1α
  • neuronal survival

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