The nuclear receptor RORα exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes
- 15 December 2009
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (50), 21365-21370
- https://doi.org/10.1073/pnas.0911782106
Abstract
Astrocytes and one of their products, IL-6, not only support neurons but also mediate inflammation in the brain. Retinoid-related orphan receptor-alpha (RORalpha) transcription factor has related roles, being neuro-protective and, in peripheral tissues, anti-inflammatory. We examined the relation of ROR(alpha) to astrocytes and IL-6 using normal and ROR(alpha) loss-of-function mutant mice. We have shown ROR(alpha) expression in astrocytes and its up-regulation by pro-inflammatory cytokines. We have also demonstrated that ROR(alpha) directly trans-activates the Il-6 gene. We suggest that this direct control is necessary to maintain IL-6 basal level in the brain and may be a link between the neuro-supportive roles of ROR(alpha), IL-6, and astrocytes. Furthermore, after inflammatory stimulation, the absence of ROR(alpha) results in excessive IL-6 up-regulation, indicating that ROR(alpha) exerts an indirect repression probably via the inhibition of the NF-kappaB signaling. Thus, our findings indicate that ROR(alpha) is a pluripotent molecular player in constitutive and adaptive astrocyte physiology.Keywords
This publication has 44 references indexed in Scilit:
- A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and FunctionJournal of Neuroscience, 2008
- Microglia repetitively isolated from in vitro mixed glial cultures retain their initial phenotypeJournal of Neuroscience Methods, 2007
- Retinoid-Related Orphan Receptor α Controls the Early Steps of Purkinje Cell Dendritic DifferentiationJournal of Neuroscience, 2006
- Enhanced susceptibility ofstaggerer(RORαsg/sg) mice to lipopolysaccharide-induced lung inflammationAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Immunohistochemical Characterization of the Orphan Nuclear Receptor RORα in the Mouse Nervous SystemJournal of Histochemistry & Cytochemistry, 2004
- RORα1 and RORα4 suppress TNF-α-induced VCAM-1 and ICAM-1 expression in human endothelial cellsFEBS Letters, 2003
- Retinoic acid receptor-related orphan receptor (ROR) α4 is the predominant isoform of the nuclear receptor RORα in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cellsBiochemical Journal, 2002
- Astroglia induce neurogenesis from adult neural stem cellsNature, 2002
- Expression and regulation of the nuclear receptor RORα in human vascular cellsFEBS Letters, 2001
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001