The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. - Archive ouverte HAL
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2009

The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes.

Nathalie Journiac
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Sarah Jolly
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Christopher Jarvis
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Vanessa Gautheron
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Monique Rogard
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Alain Trembleau
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Jean-Paul Blondeau
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Jean Mariani
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Résumé

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.

Domaines

Neurosciences

Dates et versions

hal-00490018 , version 1 (07-06-2010)

Identifiants

Citer

Nathalie Journiac, Sarah Jolly, Christopher Jarvis, Vanessa Gautheron, Monique Rogard, et al.. The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes.. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (50), pp.21365-70. ⟨10.1073/pnas.0911782106⟩. ⟨hal-00490018⟩
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