%0 Journal Article
%T Cyclooxygenase-2 is a neuronal target gene of NF-百B
%A Barbara Kaltschmidt
%A Ralf A Linker
%A Jinbo Deng
%A Christian Kaltschmidt
%J BMC Molecular Biology
%D 2002
%I BioMed Central
%R 10.1186/1471-2199-3-16
%X We have identified the neuronal cyclooxygenase-2 (COX-2) as a NF-百B target gene. In organotypic hippocampal slice cultures constitutive NF-百B activity was detected, which was correlated with high anti-COX-2 immunoreactivity. Aspirin a frequently used painkiller inhibits neuronal NF-百B activity in organotypic cultures resulting in a strong inhibition of the NF-百B target gene COX-2. Based on these findings, the transcriptional regulation of COX-2 by NF-百B was investigated. Transient transfections showed a significant increase of COX-2 promoter activity upon stimulation with PMA, an effect which could be obtained also by cotransfection of the NF-百B subunits p65 and p50. In the murine neuroblastoma cell line NB-4, which is characterized by constitutive NF-百B activity, COX-2 promoter activity could not be further increased with PMA or TNF. Constitutive promoter activity could be repressed upon cotransfection of the inhibitory subunit I百B-汐. EMSA and mutational analysis conferred the regulatory NF-百B activity to the promoter distal 百B-site in the human COX-2 promoter.NF-百B regulates neuronal COX-2 gene expression, and acts as an upstream target of Aspirin. This extends Aspirin's mode of action from a covalent modification of COX-2 to the upstream regulation of COX-2 gene expression in neurons.NF-百B a transcription factor with inducible activity, present in most cell types. This factor is crucially involved in regulation of genes relevant in neuronal survival, inflammmatory response, cancer and innate immunity [1,2]. The activation of NF-百B is mainly controlled at the posttranscriptional level by complex formation with the inhibitory subunit I百B in the cytoplasm [3]. Phosphorylation of I百B prior to degradation is catalyzed by the activation of a complex consisting of two kinases (IKK-汐 and IKK-汕) [4] together with a modifying subunit called NEMO [5] or IKK-污 [6]. Binding of NEMO is important to mediate the cytokine response in a aktivation of the kinases [7]. Recently it w
%U http://www.biomedcentral.com/1471-2199/3/16