title: The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes.
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.
authors: Unité Mixte de Recherche 7102, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, 75005 Paris, France.
authors: Nathalie
authors: N
authors: Journiac
authors: Sarah
authors: S
authors: Jolly
authors: Christopher
authors: C
authors: Jarvis
authors: Vanessa
authors: V
authors: Gautheron
authors: Monique
authors: M
authors: Rogard
authors: Alain
authors: A
authors: Trembleau
authors: Jean-Paul
authors: JP
authors: Blondeau
authors: Jean
authors: J
authors: Mariani
authors: Béatrice
authors: B
authors: Vernet-der Garabedian
mesh_terms: 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
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539739:Rora protein, mouse