Cyclooxygenase-2 is a neuronal target gene of NF-κB

• Published in: BMC molecular biology 2002-12, Vol.3 (1), p.16-16, Article 16
• Main Authors: Kaltschmidt, Barbara, Linker, Ralf A, Deng, Jinbo, Kaltschmidt, Christian
• Format: Article
• Language: English
• ISSN: 1471-2199; 1471-2199
• DOI: 10.1186/1471-2199-3-16

NF-κ B is implicated in gene regulation involved in neuronal survival, inflammmatory response and cancer. There are relatively few neuronal target genes of NF-κ B characterized. We have identified the neuronal cyclooxygenase-2 (COX-2) as a NF-κ B target gene. In organotypic hippocampal slice cultures constitutive NF-κ B activity was detected, which was correlated with high anti-COX-2 immunoreactivity. Aspirin a frequently used painkiller inhibits neuronal NF-κ B activity in organotypic cultures resulting in a strong inhibition of the NF-κ B target gene COX-2. Based on these findings, the transcriptional regulation of COX-2 by NF-κ 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-κ B subunits p65 and p50. In the murine neuroblastoma cell line NB-4, which is characterized by constitutive NF-κ 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 Iκ B- alpha . EMSA and mutational analysis conferred the regulatory NF-κ B activity to the promoter distal κ B-site in the human COX-2 promoter. NF-κ 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.