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The Journal of Neuroscience, July 1, 1999, 19(13):5236-5244
Interleukin-6 (IL-6) Production by Astrocytes: Autocrine
Regulation by IL-6 and the Soluble IL-6 Receptor
Nicholas J.
Van Wagoner,
Jae-Wook
Oh,
Pavle
Repovic, and
Etty N.
Benveniste
Department of Cell Biology, The University of Alabama at
Birmingham, Birmingham, AL 35294-0005
In the CNS, astrocytes are a major inducible source of
interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally
detrimental, adding to the pathophysiology associated with CNS
disorders. Many factors have been shown to induce IL-6 expression by
astrocytes, particularly the cytokines tumor necrosis factor-
(TNF-) and interleukin-1  (IL-1). However, the role of IL-6 in
its own regulation in astrocytes has not been determined. In this
study, we examined the influence of IL-6 alone or in combination with
TNF- or IL-1 on IL-6 expression. IL-6 alone had no effect on IL-6
expression; however, the addition of the soluble IL-6 receptor (sIL-6R)
induced IL-6 transcripts. Addition of TNF- or IL-1 plus
IL-6/sIL-6R led to synergistic increases in IL-6 expression. This
synergy also occurred in the absence of exogenously added IL-6,
attributable to TNF-- or IL-1-induced endogenous IL-6 protein
production. IL-6 upregulation seen in the presence of TNF- or
IL-1 plus IL-6/sIL-6R was transcriptional, based on nuclear run-on
analysis. Experiments were extended to other IL-6 family members to
determine their role in IL-6 regulation in astrocytes. Oncostatin M
(OSM) induced IL-6 alone and synergized with TNF- for enhanced
expression. These results demonstrate that IL-6/sIL-6R and OSM play an
important role in the regulation of IL-6 expression within the CNS,
particularly in conjunction with the proinflammatory cytokines TNF-
and IL-1.
Key words:
glial cells; cytokines; interleukin-6; central nervous
system; receptors; astrocytes
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135236-09$05.00/0
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