Characterization of a cyclooxygenase-2-765G-->C promoter polymorphism in human neural cells.
Direct sequencing of the human cyclooxygenase-2 gene promoter revealed a common single nucleotide substitution, cyclooxygenase-2-765G-->C, in 24.5% of the populations analyzed. This change introduced a 20 base pair polypyrimidine/polypurine element and a partial recognition feature for RXRalpha, the 9-cis retinoic acid receptor, into the polymorphic promoter. Cyclooxygenase-2-765G-->C constructs, when transfected into human neural cells, exhibited a 1.4-fold higher level of basal expression, while the proinflammatory factors interleukin-1beta and 9-cis retinoic acid synergistically induced polymorphic promoter activity 2.4-fold over wild type. These results suggest that under specific conditions of cellular stress, a common variation in cyclooxygenase-2 promoter structure may enhance cyclooxygenase-2 transcription, and this may contribute to the proliferation of an inflammatory response in brain cells.
Cui
Jian-Guo
JG
Neuroscience Center, Louisiana State University School of Medicine, New Orleans, Louisiana, USA.
Salehi-Rad
Shabnam
S
Rogaeva
Ekaterina
E
Lukiw
Walter J
WJ
D001483:Base Sequence; D001927:Brain Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009443:Neuritis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D014162:Transfection
D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases