IL-1β potently stabilizes IL-6 mRNA in human astrocytes

Anneleen Spooren (1) , Pieter Mestdagh (2) , Pieter Rondou (2) , Krzysztof Kolmus (1) , Guy Haegeman (1) , Sarah Gerlo (1)

1 UGENT - Universiteit Gent = Ghent University
2 Ghent University Hospital

Uncontrolled expression of IL-6 in the central nervous system is associated with neurodegenerative pathology and glioma development. Astrocytes are the predominant source of IL-6 in the central nervous system, and they are characteristically susceptible to synergistic IL-6 expression. Combined β-adrenergic and TNF-receptor triggering induces synergistic IL-6 expression in 1321N1 cells via a transcriptional enhancer mechanism. Here, we have investigated the molecular basis of the very potent "super"-synergistic IL-6 expression that is apparent after combined treatment of astrocytes with a β-adrenergic agonist, isoproterenol, and the inflammatory cytokines TNF-α and IL-1β. We found that IL-1β treatment strengthens the IL-6 synergy by inducing a distinct stabilization of IL-6 mRNA. Surprisingly, the mRNA-stabilizing effect seems to be dependent on protein kinase C (PKC), but not on the prototypical mRNA-stabilizing kinase p38. Moreover, although the mRNA-binding protein HuR basally stabilizes IL-6 mRNA, the mRNA-stabilizing effect of IL-1β is independent of HuR. Our data using pharmacological inhibitors suggest PKC is an important modulator of IL-6 expression in the central nervous system and this might have therapeutic implications.

Mots clés: mRNA stability; IL-6; astrocytes; IL-1β; PKC; p38

Domaines: Pharmacologie

Anneleen Spooren, Pieter Mestdagh, Pieter Rondou, Krzysztof Kolmus, Guy Haegeman, et al.. IL-1β potently stabilizes IL-6 mRNA in human astrocytes. Biochemical Pharmacology, 2011, ⟨10.1016/j.bcp.2011.01.019⟩. ⟨hal-00681627⟩