The nuclear factor-B (NF-B) is an important transcription factor necessary for initiating and sustaining inflammatory and immune reactions. The inducers of NF-B are well characterized, but the molecular mechanisms underlying multiple in vivo NF-B activation processes are poorly understood. The injection of lipopolysaccharide resulted in a biphasic activation of NF-B during the 18-h observation period in various organs of mice. The early and late phases of NF-B activation occurred at 0.5-2 h and

more »

... 8 -12 h, respectively. Platelet-activating factor, which is released in response to lipopolysaccharide injection, was responsible for the activation of the early phase of NF-B. The early NF-B activity led to the induction of proinflammatory cytokines, tumor necrosis factor (TNF), and interleukin (IL)-1␤, which are known to be efficient inducers of NF-B. Using the TNF knockout and IL-1 receptor knockout mice, we found that TNF and IL-1␤ had a role in the second phase activation of NF-B. These cytokines did promote the synthesis of platelet-activating factor, which in turn induced the secondary activation of NF-B. These observations describe a novel autoregulatory molecular mechanism for the biphasic activation of NF-B.