TY - JOUR
T1 - IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia
AU - Liu, Judy S.H.
AU - Amaral, Terry D.
AU - Brosnan, Celia F.
AU - Lee, Sunhee C.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/8/15
Y1 - 1998/8/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9712071
AN - SCOPUS:0032529205
SN - 0022-1767
VL - 161
SP - 1989
EP - 1996
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -