Category: signaling
Master inflammation + survival transcription factor pathway. Resting state: NF-κB heterodimer (p50/p65) sequestered in cytoplasm bound to IκB. Activation by TLR / TNF / IL-1 / antigen receptor signaling → IKK complex phosphorylates IκB → IκB ubiquitinated + proteasomally degraded → NF-κB translocates to nucleus → drives transcription of cytokines (TNF, IL-6, IL-1β), adhesion molecules, anti-apoptotic genes (BCL-2 family), COX-2, iNOS. Glucocorticoids inhibit NF-κB via transrepression (GR-NF-κB direct interaction) — the explanation for their broad anti-inflammatory action. NSAIDs work downstream (block COX-2 product); steroids work upstream.