The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes.
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.
Journiac
Nathalie
N
Unité Mixte de Recherche 7102, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, 75005 Paris, France.
Jolly
Sarah
S
Jarvis
Christopher
C
Gautheron
Vanessa
V
Rogard
Monique
M
Trembleau
Alain
A
Blondeau
Jean-Paul
JP
Mariani
Jean
J
Vernet-der Garabedian
Béatrice
B
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001923:Brain Chemistry; D016207:Cytokines / Q000502:physiology; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000235:genetics
D016207:Cytokines; D015850:Interleukin-6; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539739:Rora protein, mouse