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.
Han
Su-Ji
SJ
Department of Biological Sciences, College of Natural Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju 500-757, Republic of Korea.
Ko
Hyun-Mi
HM
Choi
Jung-Hwa
JH
Seo
Kook Heon
KH
Lee
Hyun-Suk
HS
Choi
Eun-Kyoung
EK
Choi
Il-Whan
IW
Lee
Hern-Ku
HK
Im
Suhn-Young
SY
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D001381:Azepines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D017472:Receptors, Interleukin-1; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C053321:CV 6209; C064509:BN 50739