Human glutathione dependent prostaglandin E synthase: gene structure and regulation

A PI clone containing the gene for human glutathione dependent PGE synthase (PGES) was isolated and characterized. The gene is divided into three exon s, spans 14.8 kb and was localized to chromosome 9q34.3. In A549 cells, the protein and activity levels of PGES were increased by interleukin-1 beta. This increase was prevented by phenobarbital, Reporter constructs containin g the 5'-flanking region of exon 1, which exhibited strong promoter activit y, responded accordingly, except that interleukin-lp induced a transient in crease followed by a decrease. As cyclooxygenase 2 expression has been repo rted to respond in a similar fashion, a transcriptional regulatory basis fo r the observed co-regulation with PGES is implied. The strong down-regulati on by phenobarbital raises important issues concerning its mechanisms of ac tion. (C) 2000 Federation of European Biochemical Societies.