The article by Timothy Hla and Karen Neilson describes the cloning, sequencing, and expression of human cyclooxygenase-2 (Cox-2) cDNA. Cox-2, also known as prostaglandin H synthase, is a key enzyme in the production of inflammatory prostaglandins. The authors cloned the second form of the Cox gene (Cox-2) from human umbilical vein endothelial cells (HUVEC). The cDNA encodes a polypeptide of 604 amino acids that shares 61% identity with the previously isolated human Cox-1 polypeptide. In vitro translation of the human Cox-2 transcript in rabbit reticulocyte lysates resulted in the synthesis of a 70-kDa protein immunoprecipitated by antiserum to ovine Cox. Expression of the hCox-2 open reading frame in Cos-7 monkey kidney cells resulted in the formation of cyclooxygenase activity. hCox-2 cDNA hybridizes to a 4.5-kilobase mRNA species in HUVEC, while hCox-1 cDNA hybridizes to 3- and 5.3-kilobase species. Both Cox-1 and Cox-2 mRNAs are expressed in HUVEC, vascular smooth muscle cells, monocytes, and fibroblasts. Cox-2 mRNA was preferentially induced by phorbol 12-myristate 13-acetate and lipopolysaccharide in human endothelial cells and monocytes. These findings demonstrate that the Cox enzyme is encoded by at least two genes, Cox-1 and Cox-2, which are expressed and differentially regulated in various cell types. High-level induction of hCox-2 transcript in mesenchymal-derived inflammatory cells suggests a role in inflammatory conditions.The article by Timothy Hla and Karen Neilson describes the cloning, sequencing, and expression of human cyclooxygenase-2 (Cox-2) cDNA. Cox-2, also known as prostaglandin H synthase, is a key enzyme in the production of inflammatory prostaglandins. The authors cloned the second form of the Cox gene (Cox-2) from human umbilical vein endothelial cells (HUVEC). The cDNA encodes a polypeptide of 604 amino acids that shares 61% identity with the previously isolated human Cox-1 polypeptide. In vitro translation of the human Cox-2 transcript in rabbit reticulocyte lysates resulted in the synthesis of a 70-kDa protein immunoprecipitated by antiserum to ovine Cox. Expression of the hCox-2 open reading frame in Cos-7 monkey kidney cells resulted in the formation of cyclooxygenase activity. hCox-2 cDNA hybridizes to a 4.5-kilobase mRNA species in HUVEC, while hCox-1 cDNA hybridizes to 3- and 5.3-kilobase species. Both Cox-1 and Cox-2 mRNAs are expressed in HUVEC, vascular smooth muscle cells, monocytes, and fibroblasts. Cox-2 mRNA was preferentially induced by phorbol 12-myristate 13-acetate and lipopolysaccharide in human endothelial cells and monocytes. These findings demonstrate that the Cox enzyme is encoded by at least two genes, Cox-1 and Cox-2, which are expressed and differentially regulated in various cell types. High-level induction of hCox-2 transcript in mesenchymal-derived inflammatory cells suggests a role in inflammatory conditions.