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J. Biol. Chem., Vol. 277, Issue 47, 44715-44721, November 22, 2002

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Molecular Mechanisms for Lipopolysaccharide-induced Biphasic Activation of Nuclear Factor-B (NF-B)^*

Su-Ji Han, Hyun-Mi Ko, Jung-Hwa Choi, Kook Heon Seo, Hyun-Suk Lee, Eun-Kyoung Choi, Il-Whan Choi^§, Hern-Ku Lee^§, and Suhn-Young Im^¶

From the  Department of Biological Sciences, College of Natural Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju 500-757, Korea and the ^§ Department of Immunology and Institute for Medical Sciences, Chonbuk National University Medical School, Chonju 561-182, Republic of Korea

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 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.

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