IL-12 Production by Central Nervous System Microglia is Inhibited by Astrocytes

Francesca Aloisi, Giuseppe Penna, Joanna Cerase, B. M. Iglesias, Luciano Adorini

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

IL-12, a 75-kDa heterodimeric cytokine composed of two chains (p35 and p40), is a central regulator of immune responses and may be implicated in the pathogenesis of certain inflammatory diseases of the central nervous system (CNS). We have examined the capacity of two CNS APC, microglia and astrocytes, to produce IL-12 upon stimulation with cytokines, LPS, or a neurotropic virus. In purified microglial cultures from neonatal mouse brains, expression of IL-12 p35 and p40 mRNA is induced by LPS and is stimulated maximally by combined IFN-γ/LPS treatment, as detected by semiquantitative reverse-transcriptase PCR. LPS induces secretion of IL-12 p40, but not of IL-12 p75, as detected by specific ELISA. Combined stimulation with IFN-γ/LPS enhances IL-12 p40 secretion and induces IL-12 p75 secretion by microglia. Conversely, mouse astrocytes do not express IL-12 p35 mRNA and do not secrete IL-12 p75 under any condition tested. IL-12 production by activated microglia is inhibited by IL-10, PGE2, and cAMP-elevating agents. Coculture of microglia with astrocytes or exposure of microglia to astrocyte-conditioned medium also results in marked reduction of IL-12 p75 and p40 secretion by IFN-γ/LPS-stimulated microglia, indicating a regulatory role of astrocytes on IL-12 production. This novel mechanism of IL-12 regulation may play an important role in the control of immune responses during infection or in Th1 cell-mediated autoimmune diseases of the CNS.

Original languageEnglish
Pages (from-to)1604-1612
Number of pages9
JournalJournal of Immunology
Volume159
Issue number4
Publication statusPublished - Aug 15 1997

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Microglia
Interleukin-12
Astrocytes
Central Nervous System
Autoimmune Diseases of the Nervous System
Cytokines
Messenger RNA
Th1 Cells
Central Nervous System Diseases
Conditioned Culture Medium
Coculture Techniques
Reverse Transcriptase Polymerase Chain Reaction
Dinoprostone
Interleukin-10
Enzyme-Linked Immunosorbent Assay
adjuvant P40

ASJC Scopus subject areas

  • Immunology

Cite this

Aloisi, F., Penna, G., Cerase, J., Iglesias, B. M., & Adorini, L. (1997). IL-12 Production by Central Nervous System Microglia is Inhibited by Astrocytes. Journal of Immunology, 159(4), 1604-1612.

IL-12 Production by Central Nervous System Microglia is Inhibited by Astrocytes. / Aloisi, Francesca; Penna, Giuseppe; Cerase, Joanna; Iglesias, B. M.; Adorini, Luciano.

In: Journal of Immunology, Vol. 159, No. 4, 15.08.1997, p. 1604-1612.

Research output: Contribution to journalArticle

Aloisi, F, Penna, G, Cerase, J, Iglesias, BM & Adorini, L 1997, 'IL-12 Production by Central Nervous System Microglia is Inhibited by Astrocytes', Journal of Immunology, vol. 159, no. 4, pp. 1604-1612.
Aloisi F, Penna G, Cerase J, Iglesias BM, Adorini L. IL-12 Production by Central Nervous System Microglia is Inhibited by Astrocytes. Journal of Immunology. 1997 Aug 15;159(4):1604-1612.
Aloisi, Francesca ; Penna, Giuseppe ; Cerase, Joanna ; Iglesias, B. M. ; Adorini, Luciano. / IL-12 Production by Central Nervous System Microglia is Inhibited by Astrocytes. In: Journal of Immunology. 1997 ; Vol. 159, No. 4. pp. 1604-1612.
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