Interleukin-1 beta induces cyclooxygenase-2 gene expression in cultured endometrial stromal cells

J Clin Endocrinol Metab. 1998 Feb;83(2):538-41. doi: 10.1210/jcem.83.2.4533.

Abstract

Increasing evidence indicates that PGs may play an obligatory role in blastocyst implantation. Cyclooxygenase (also known as PGH synthase) isozymes 1 and 2 catalyze the rate limiting steps in the biosynthesis of PGs. The ubiquitous cyclooxygenase-1 (COX-1) subserves housekeeping functions, whereas the inducible cyclooxygenase-2 (COX-2) is expressed by limited cell types and tightly controlled. Here we report the induction of COX-2 gene expression by interleukin-1 beta (IL-1 beta) in cultured human endometrial stromal cells. COX-2 activity was induced by IL-1 beta (1 ng/mL); conversion of exogenous arachidonic acid to PGF2 alpha increased from 2.6 +/- 0.6 ng/well (mean +/- SEM; n = 6) to 22.2 +/- 5.6 ng, but was completely blocked (2.8 +/- 0.7 ng/well) by NS-398, a specific COX-2 inhibitor. Undetectable in quiescent stromal cells, messenger ribonucleic acid for COX-2 was induced 30 min after IL-1 beta treatment, reached a maximum at 4 h, and decreased after 15 h. Protein synthesis was not required for induction of the COX-2 gene, as it was blocked by actinomycin D but not by cycloheximide. The 70-kDa COX-2 protein was not detected in quiescent cells, became detectable 6 h after IL-1 beta treatment, and remained detectable even after 15 h. IL-1 beta (0.1-100 ng/mL) increased the luciferase activity in promoterless luciferase reporter containing the 900-bp 5'-flanking sequence (-891 to +9) of the COX-2 gene in a dose-dependent manner, with an ED50 of 0.1-1 ng/mL.

MeSH terms

  • Arachidonic Acid / metabolism
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Dinoprost / metabolism
  • Endometrium / enzymology*
  • Female
  • Gene Expression*
  • Humans
  • Interleukin-1 / pharmacology*
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Kinetics
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / biosynthesis
  • Stromal Cells / enzymology*

Substances

  • Interleukin-1
  • Isoenzymes
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Dactinomycin
  • Arachidonic Acid
  • Cycloheximide
  • Dinoprost
  • Prostaglandin-Endoperoxide Synthases