Prostaglandin G/H synthase-2 is the constitutive and dominant isoform in cultured human lung epithelial cells.
Two isoforms of prostaglandin G/H synthase (PGHS; prostaglandin endoperoxide synthase, cyclooxygenase) have been identified; PGHS-1 is expressed constitutively in most tissues, whereas PGHS-2 is thought to be induced by various proinflammatory cytokines and growth factors. In this study, we determined which isoform of PGHS mRNA, protein, and activity was present constitutively in A549 (a human lung adenocarcinoma cell line) and in untransformed (normal human bronchial epithelial or NHBE) and transformed (16HBE4o-) human bronchial epithelial cells. Two PGHS-2-specific inhibitors, NS-398 and L-745, 337, blocked the release of prostaglandin E2 from A549 cells with mean inhibitory concentrations of 5 and 18 nM, respectively, but did not inhibit its release from human bronchial smooth muscle cells (BSMC) at a concentration of 10 microM. Northern and immunoblot analysis demonstrated that BSMC expressed PGHS-1 mRNA and protein constitutively, whereas epithelial cells expressed PGHS-2 mRNA and protein constitutively with either undetectable (A549, 16HBE4o-) or very low levels (NHBE) of PGHS-1. We conclude that PGHS-2 is the dominant PGHS isoform in unstimulated and stimulated lung epithelial cells in culture.
Asano
K
K
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Lilly
C M
CM
Drazen
J M
JM
D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D007527:Isoenzymes; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone