AI Article Synopsis
- Uncontrolled IL-6 expression in the central nervous system is linked to neurodegenerative diseases and glioma development, with astrocytes being the main source of IL-6.
- A combination of β-adrenergic activation and inflammatory cytokines like TNF-α and IL-1β leads to a very strong synergistic effect on IL-6 production in astrocytes through a specific transcriptional mechanism.
- The study shows that IL-1β enhances IL-6 mRNA stability via a protein kinase C-dependent pathway, suggesting that targeting PKC could have potential therapeutic benefits in managing IL-6 related conditions in the brain.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.bcp.2011.01.019 | DOI Listing |
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