Bourke, Emer and Moynagh, Paul N. (1999) Antiinflammatory Effects of Glucocorticoids in Brain Cells, Independent of NF-kB. Journal of Immunology, 163. pp. 2113-2119. ISSN 0022-1767

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Abstract

Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein IkB, which inhibits the transcription factor NF-kB. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce IkB or inhibit activation of NF-kB by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kB by demonstrating that an oligonucleotide, containing the wild-type NF-kB-binding motif, inhibited formation of the NF-kB-DNA complexes whereas a mutated form of the NF-kB-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kB complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kB correlated with its inability to induce IkB and the ability of IL-1 to cause degradation of IkB, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kB.

Item Type:	Article
Keywords:	Antiinflammatory Effects; Glucocorticoids; Brain Cells; NF-kB; antiinflammatory drugs; proinflammatory cytokines; adhesion molecules;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7222
Depositing User:	Professor Paul Moynagh
Date Deposited:	09 Aug 2016 14:29
Journal or Publication Title:	Journal of Immunology
Publisher:	American Association of Immunologists
Refereed:	Yes
Funders:	Health Research Board (HRB), European Commission Fourth Framework Biotechnology Program (BIO4 CT96 0246).
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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