IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia

Judy S H Liu, Terry D. Amaral, Celia F. Brosnan, Sunhee C. Lee

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Abstract

Because IL-1 is implicated in the pathogenesis of multiple sclerosis, and IFNs are known to alter disease course, we sought to determine whether IFNs can regulate the expression of IL-1 and IL-1R antagonist (IL-1Ra) in primary cultures of human microglia and astrocytes. We found that IL-1 and IL-1Ra are products of microglia but not astrocytes, and IFN-β and IFN-γ differentially modulate LPS- and cytokine-induced IL-1 and IL-1Ra. IFN-β induces IL-1Ra and augments LPS- and IL-4-induced IL-1Ra, but suppresses LPS- and IL-1-induced IL-1, shifting the balance toward the expression of the IL- 1Ra. Like IFN-β, IFN-γ suppresses the expression of both LPS and IL-1- induced IL-1β. However, IFN-γ also suppresses the expression of IFN-β and IL-4-induced IL-1Ra so that IFN-γ may enhance or suppress IL-1 activity depending on the other cytokines present. IL-4 has similar effects to IFN- β; however, other anti-inflammatory cytokines, did not regulate IL-1 or IL- 1Ra in human microglia. Our data demonstrate a novel suppressive effect of IFN-β and IL-4 on IL-1 activity in human microglia, suggesting that IFN-β, a therapeutic agent used for multiple sclerosis, could have wider applications in the treatment of other central nervous system disorders in which IL-1 activity has been implicated in the pathogenesis.

Original languageEnglish (US)
Pages (from-to)1989-1996
Number of pages8
JournalJournal of Immunology
Volume161
Issue number4
StatePublished - Aug 15 1998

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Interleukin-1 Receptors
Microglia
Interleukin-1
Interleukin-4
Interleukin 1 Receptor Antagonist Protein
Cytokines
Astrocytes
Multiple Sclerosis
Central Nervous System Diseases
Human Activities
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Immunology

Cite this

Liu, J. S. H., Amaral, T. D., Brosnan, C. F., & Lee, S. C. (1998). IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia. Journal of Immunology, 161(4), 1989-1996.

IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia. / Liu, Judy S H; Amaral, Terry D.; Brosnan, Celia F.; Lee, Sunhee C.

In: Journal of Immunology, Vol. 161, No. 4, 15.08.1998, p. 1989-1996.

Research output: Contribution to journalArticle

Liu, JSH, Amaral, TD, Brosnan, CF & Lee, SC 1998, 'IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia', Journal of Immunology, vol. 161, no. 4, pp. 1989-1996.
Liu, Judy S H ; Amaral, Terry D. ; Brosnan, Celia F. ; Lee, Sunhee C. / IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia. In: Journal of Immunology. 1998 ; Vol. 161, No. 4. pp. 1989-1996.
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