Molecular mechanisms for lipopolysaccharide-induced biphasic activation of nuclear factor-kappa B (NF-kappa B).

The nuclear factor-kappaB (NF-kappaB) is an important transcription factor necessary for initiating and sustaining inflammatory and immune reactions. The inducers of NF-kappaB are well characterized, but the molecular mechanisms underlying multiple in vivo NF-kappaB activation processes are poorly understood. The injection of lipopolysaccharide resulted in a biphasic activation of NF-kappaB during the 18-h observation period in various organs of mice. The early and late phases of NF-kappaB activation occurred at 0.5-2 h and 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-kappaB. The early NF-kappaB activity led to the induction of proinflammatory cytokines, tumor necrosis factor (TNF), and interleukin (IL)-1beta, which are known to be efficient inducers of NF-kappaB. Using the TNF knockout and IL-1 receptor knockout mice, we found that TNF and IL-1beta had a role in the second phase activation of NF-kappaB. These cytokines did promote the synthesis of platelet-activating factor, which in turn induced the secondary activation of NF-kappaB. These observations describe a novel autoregulatory molecular mechanism for the biphasic activation of NF-kappaB.

Citation

Su-Ji Han, Hyun-Mi Ko, Jung-Hwa Choi, Kook Heon Seo, Hyun-Suk Lee, Eun-Kyoung Choi, Il-Whan Choi, Hern-Ku Lee, Suhn-Young Im. Molecular mechanisms for lipopolysaccharide-induced biphasic activation of nuclear factor-kappa B (NF-kappa B). The Journal of biological chemistry. 2002 Nov 22;277(47):44715-21

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PMID: 12235132

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