Inhibitory effects of resveratrol and curcumin on IL-1β-induced NF-κB activation and apoptosis in primary human chondrocytes in vitro. IL-1β stimulates the IL-1β receptor, intiating an intracellular signal transduction cascade, which activates the cytoplasmic IκBα kinases (IKK)-α, IKK-β, and IKK-γ. These kinases phosphoryle inactive IκBα. Phosphorylated IκBα is then ubiquitinated and degraded by the proteasome and active NF-κB is released. NF-κB translocates to the nucleus, where it activates proinflammatory and pro-apoptotic gene production. In chondrocytes, resveratrol and curcumin both inhibit the NF-κB signal transduction pathway but in different ways: resveratrol inhibits ubiquitination of phosphorylated IκBα, and blocks translocation of the activated NF-κB to the nucleus. In a similar fashion to resveratrol, curcumin also inhibits translocation of the activated NF-κB to the nucleus. However in contrast to resveratrol, curcumin does not have a degradation inhibiting effect on phosphorylated IκBα. Instead, curcumin inhibits IL-1β signalling at an earlier point by inhibition of IKK-α, IKK-β, and IKK-γ.