TNF- and IL-1-induced inflammation are enhanced through cooperative interactions between Nrf2 and NF-κB.

Keap1/Nrf2 redox signaling enhances TNF- and IL-1–initiated inflammatory cytokine production, with Nrf2 activation linked to stronger NF-κB (p65 RelA) activity at NF-κB promoters.

• Why it matters: Reactive oxygen is often implicated in inflammation, but the specific redox mediators that tune TNF- and IL-1–driven inflammatory outputs remain unclear.
• What they did: Inflammatory cytokine production was measured after Keap1 was silenced or deleted to boost Nrf2, and after Nrf2 activation was suppressed to reduce it; mechanistic assays tested cooperation between Nrf2 and p65 RelA at NF-κB-regulated promoters.
• The result: Enhanced or blunted TNF- or IL-1–driven cytokine production depending on Nrf2 activity indicates Nrf2 acts as a rheostat for NF-κB–dependent inflammatory outputs via cooperative promoter interactions with p65 RelA.

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