MiR-206 Modulates Lip Polysaccharide-mediated Inflammatory Cytokine Production In Human Gliaoma Cell

Astrocyte-derived inflammation is a common component of acute or chronic injury in the central nervous system. Micro RNAs(micro RNAs) are small non-coding RNAs that play important regulatory roles in the inflammatory response. In this study, we found that mi R-206 is induced upon stimulation with lipopolysaccharide. Overexpression of mi R-206 in astrocytes led to increased expression of inflammatory cytokines(interleukin-6, interleukin-1β, CCL5) upon exposure to lipopolysaccharide, whereas knockdown of mi R-206 had completely opposite effects. We used a combination of bioinformatics and experimental techniques to demonstrate that NR4A2, which belongs to the nuclear receptor(NR) 4 family of orphan nuclear receptors, is a direct target of mi R-206. Overexpression of mi R-206 mimics decreased the activity of a luciferase reporter containing the NR4A2 3′-untranslated region and led to decreased NR4A2 m RNA and protein levels. In contrast, ectopic expression of an mi R-206 inhibitor led to elevated NR4A2 expression. We also found that mi R-206 modulated the lipopolysaccharide-induced proinflammatory response by targeting NR4A2 and activating nuclear factor-kappa B activity. Finally, we demonstrated that the transcription factor AP-1 plays a critical role in lipopolysaccharide-induced expression of mi R-206 and that the extracellular signal–regulated kinase signaling pathway contributes to the regulation of mi R-206 level in astrocytes. These data demonstrate that mi R-206 positively regulates the lipopolysaccharide-induced inflammatory response in human astrocytes.