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Interleukin‐1 alpha and vasoactive interstinal peptide: Enigmatic regulation of neuronal survival
Author(s) -
Brenneman D.E.,
Hill J.M.,
Glazner G.W.,
Gozes I.,
Phillips T.W.
Publication year - 1995
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(95)00014-8
Subject(s) - vasoactive intestinal peptide , neurotrophin , antiserum , alpha (finance) , receptor , endocrinology , neurotrophic factors , medicine , substance p , biology , neuropeptide , immunology , antibody , construct validity , nursing , patient satisfaction
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.