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Fig. 11 | Journal of Neuroinflammation

Fig. 11

From: 6-Mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation

Fig. 11

Proposed model for 6-MP inhibition of LPS-induced TNF-α expression. Release of NF-κB dimmers following LPS stimulation is linked to phosphorylation of p65 at Ser276, either in the cytoplasm by PKAc or in the nucleus by MSK1. In microglia, 6-MP upregulates Nur77 expression. Nur77 subsequently attenuates p65 phosphorylation (S276) by inhibiting a yet unidentified kinase and acetylation (K310) by dampening p300 activity to limit transcriptional activation of p65. Furthermore, Nur77 blocks the acetylation of histone H3 at TNF-α promoter, ultimately leading to compacting chromatin structures and impairing binding of p65. Both events reduce the LPS-induced TNF-α gene transcription. On the other hand, the inhibitory action of 6-MP also occurs via inactivation of PI3K/Akt/mTOR signaling to downregulate translation

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Journal of Neuroinflammation

ISSN: 1742-2094