Interleukin-1 beta induces cytosolic phospholipase A2 and prostaglandin H synthase in rheumatoid synovial fibroblasts. Evidence for their roles in the production of prostaglandin E2

Arthritis Rheum. 1994 May;37(5):653-61. doi: 10.1002/art.1780370508.


Objective: In order to investigate potential regulatory mechanisms for the increased production of prostaglandin E2 (PGE2) in interleukin-1 beta (IL-1 beta)-stimulated rheumatoid synovial fibroblasts (RSF), this study examined the induction of phospholipase A2 (PLA2) and prostaglandin H synthase (PGHS) enzymes and the correlation of these events with PGE2 production in IL-1 beta-stimulated RSF.

Methods: Protein and messenger RNA (mRNA) levels of cytosolic PLA2 (cPLA2) and PGHS-2 enzymes in IL-1 beta-stimulated RSF were measured by Western and Northern blotting, respectively, using specific antisera and complementary DNA probes. Enzymatic activity of cPLA2 was determined in cell-free reaction mixtures utilizing mixed micelles of 14C-phosphatidylcholine and Triton X-100 as the substrate. PGE2 levels were quantitated using a commercial enzyme immunoassay kit.

Results: Incubation of RSF with IL-1 beta increased the mRNA and protein levels for the high molecular weight cPLA2 as well as for the mitogen/growth factor-responsive PGHS (PGHS-2). The IL-1 receptor antagonist completely abolished the induction of these two enzymes and the stimulation of PGE2 production by IL-1 beta in RSF. In contrast, levels of the other known forms of these enzymes, i.e., the 14-kd secretory group II PLA2 (sPLA2) and the constitutive form of PGHS (PGHS-1), were unaffected by IL-1 beta treatment.

Conclusion: These are the first data to demonstrate the coordinate induction by IL-1 of cPLA2 and PGHS-2 in RSF. The time-course for the induction of these enzymes suggests that their increase contributes to the increased production of PGE2 in IL-1-treated RSF, and may help explain the capacity of RSF to produce large amounts of PGE2.

MeSH terms

  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Cytosol / enzymology*
  • Dinoprostone / biosynthesis*
  • Fibroblasts / enzymology*
  • Humans
  • Interleukin-1 / immunology*
  • Phospholipases A / genetics
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / analysis
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism*
  • Up-Regulation / physiology


  • Interleukin-1
  • RNA, Messenger
  • Prostaglandin-Endoperoxide Synthases
  • Phospholipases A
  • Phospholipases A2
  • Dinoprostone