Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes

Francesca Aloisi, Silvia Rosa, Ugo Testa, Paola Bonsi, Giovanni Russo, Cesare Peschle, Giulio Levi

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Abstract

We have examined the ability of human astrocytes to synthesize and secrete leukemia inhibitory factor (LIF), which is a multifunctional cytokine that controls cell proliferation and differentiation in many tissues, including the nervous system. Astrocyte-enriched cultures, prepared from 8- to 9-wk- old embryonic brains, expressed LIF mRNA and secreted LIF protein. LIF synthesis was significantly increased by the cytokines IL-1β, TNF-α, and TGF-β1, but not by IFN-γ, IL-6, or LPS. No major differences in basal and cytokine-inducible LIF production were detected among astrocyte populations obtained from different brain areas. LIF synthesis was lower in serum-free than in serum-containing astrocyte cultures. A role for protein kinase C in the regulation of astrocyte LIF production was suggested by the findings that phorbol esters induced both LIF mRNA and protein and that the cytokine- induced LIF increase was partially antagonized by relatively selective inhibitors of protein kinase C such as H7 and staurosporine. Human leptomeningeal fibroblasts also expressed LIF gene and protein. Astrocytes produced LIF and responded to cytokines with increased LIF synthesis only after being subcultured, and not when grown in primary cultures in close contact with neurons. Our findings suggest that in vivo induction of astrocyte LIF secretion might occur in pathologic conditions as a consequence of both alterations of neuronal-glial interactions and a local increase in the level of inflammatory cytokines.

Original languageEnglish
Pages (from-to)5022-5031
Number of pages10
JournalJournal of Immunology
Volume152
Issue number10
Publication statusPublished - May 15 1994

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Leukemia Inhibitory Factor
Astrocytes
Cytokines
Protein Kinase C
Messenger RNA
Proteins
Staurosporine
Brain
Phorbol Esters
Serum
Interleukin-1
Neuroglia
Nervous System
Cell Differentiation

ASJC Scopus subject areas

  • Immunology

Cite this

Aloisi, F., Rosa, S., Testa, U., Bonsi, P., Russo, G., Peschle, C., & Levi, G. (1994). Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes. Journal of Immunology, 152(10), 5022-5031.

Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes. / Aloisi, Francesca; Rosa, Silvia; Testa, Ugo; Bonsi, Paola; Russo, Giovanni; Peschle, Cesare; Levi, Giulio.

In: Journal of Immunology, Vol. 152, No. 10, 15.05.1994, p. 5022-5031.

Research output: Contribution to journalArticle

Aloisi, F, Rosa, S, Testa, U, Bonsi, P, Russo, G, Peschle, C & Levi, G 1994, 'Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes', Journal of Immunology, vol. 152, no. 10, pp. 5022-5031.
Aloisi F, Rosa S, Testa U, Bonsi P, Russo G, Peschle C et al. Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes. Journal of Immunology. 1994 May 15;152(10):5022-5031.
Aloisi, Francesca ; Rosa, Silvia ; Testa, Ugo ; Bonsi, Paola ; Russo, Giovanni ; Peschle, Cesare ; Levi, Giulio. / Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes. In: Journal of Immunology. 1994 ; Vol. 152, No. 10. pp. 5022-5031.
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