Cytokine regulation of astrocyte function: in-vitro studies using cells from the human brain

Francesca Aloisi, Giobanna Borsellino, Alessandra Caré, Ugo Testa, Paolo Gallo, Giobanni Russo, Cesare Peschle, Giulio Levi

Research output: Contribution to journalArticlepeer-review

Abstract

Participation of astrocytes in central nervous system pathophysiology is likely to involve cytokines, both as stimulators and mediators of astrocyte function. We have used highly enriched human astrocyte cultures as an experimental tool to investigate the influence of cytokines on adhesion molecule expression and synthesis of mediators that are probably important in immune and inflammatory reactions involving the nervous system and in cerebral tissue repair. The response of astrocytes to interferon-γ mainly resulted in increased expression of major histocompatibility complex antigens and co-stimulatory molecules (intercellular adhesion molecule-1, LFA-1α) which mediate astrocyte-T-cell interactions. Another co-stimulatory molecule, B7, was neither expressed nor inducible by IFN-γ and other cytokines. TNF-α and IL-1β were more efficient in stimulating synthesis of immunoregulatory and proinflammatory cytokines (IL-6, IL-8 and colony-stimulating factors), cytokine antagonists (TNF-α soluble receptors), or cytokines with a possible neuroprotective role (leukemia inhibitory factor); they also increased expression of some co-stimulatory molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1). Transforming growth factor-β1 was a strong inducer of leukemia inhibitory factor, but did not affect either major histocompatibility complex/co-stimulatory molecule expression or cytokine synthesis. Thus, different cytokines activate distinct functional programs in astrocytes, which may play a specific role in different brain diseases or at different stages of the same disease. It was additionally observed that the response of human astrocytes to cytokines (in particular the inducible synthesis of certain cytokines) varied greatly depending on the presence or absence of neurons in the culture system. This finding suggests that neuronal-glial interactions may be implicated in determining the activation threshold of astrocytes to inflammatory cytokines.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalInternational Journal of Developmental Neuroscience
Volume13
Issue number3-4
DOIs
Publication statusPublished - 1995

Keywords

  • astrocytes
  • cytokines
  • inflammatory reaction

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

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