Kinase regulation in inflammatory response

The transcription factor NF-κB is a pivotal regulator of innate immune responses, whose activity is rapidly induced by proinflammatory stimuli, most notably the tumour-necrosis factor TNFα and interleukin-1, viruses, and components of bacterial cell walls1. In addition, NF-κB protects cells from the induction of programmed cell death by pro-apoptotic stimuli such as TNFα (refs 2, 3). Another important anti-apoptotic signal-transducing protein is the protein kinase Akt (also known as protein kinase B), whose activity is strongly stimulated by growth factors4. Ozes et al.5 have suggested that Akt is involved in the TNFα-mediated activation of NF-κB5, implying that some of the anti-apoptotic activity of Akt may be mediated through NF-κB. However, we have failed to detect any involvement of Akt in the signalling pathway through which TNFα leads to NF-κB activation.