Constitutive expression of prostaglandin endoperoxide G/H synthetase (PGHS)-2 but not PGHS-1 in hum an tracheal epithelial cells in vitro

Prostaglandins. 1996 Nov;52(5):341-59. doi: 10.1016/s0090-6980(96)00101-3.


Primary cultures of human tracheal epithelial (HTE) cells cultured in vitro, in defined serum-free media, express prostaglandin endoperoxide G/H synthase (PGHS) activity and produce prostaglandin E2 (PGE2). In contrast to every other cell type studied to date, HTE cells appear to constitutively express PGHS-2, the 'inducible' form of the enzyme, while expressing little or no PGHS-1, the 'housekeeping' isoenzyme in vitro. Prostaglandin synthesis in HTE cells was reduced by a selective PGHS-2 inhibitor, N-[2-cyclohexyloyl-4-nitrophenyl] methane-sulfonamide (NS398), with an IC50 of approximately 1 microM. Immunoblotting and immunoprecipitation of enzymatic activity with isozyme-specific antisera revealed only the PGHS-2 isoform. Full length human cDNA probes detected only PGHS-2 message in Northern blots. Neither PGHS-2 activity nor mRNA levels were dependent on, nor stimulated by peptide growth factors present in the defined serum-free growth medium, or by serum. Prolonged maintenance in the absence of retinoic acid, however, lead to a decline in PGHS activity. Phorbol-myristate acetate (PMA) induced PGHS-2 activity and mRNA and neither PMA-induced, nor constitutive PGHS-2 expression was suppressed by corticosteroids. Actinomycin D-treatment for six hours reduced the PGHS-2 activity and mRNA to only 50% that of untreated cells, suggesting that PGHS-2 mRNA is extremely stable in these cells. HTE cells, at least in vitro, appear unique among prostaglandin-producing cells in that they express PGHS-2, constitutively, independent of regulation by growth factors, serum, or corticosteroids and fail to express PGHS-1 under any culture condition studied.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Blotting, Northern
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cycloheximide / pharmacology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Epithelial Cells
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Growth Substances / pharmacology
  • Humans
  • Immunoblotting
  • Indomethacin / pharmacology
  • Isoenzymes / biosynthesis*
  • Isoenzymes / drug effects*
  • Isoenzymes / physiology
  • Membrane Proteins
  • Nitrobenzenes / pharmacology
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Prostaglandin-Endoperoxide Synthases / physiology
  • RNA, Messenger / metabolism
  • Sulfonamides / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trachea / cytology
  • Trachea / drug effects
  • Trachea / metabolism*


  • Adrenal Cortex Hormones
  • Culture Media, Serum-Free
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Growth Substances
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cycloheximide
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Tetradecanoylphorbol Acetate
  • Indomethacin