Effects of interleukin-1beta and prostaglandin E2 on prostaglandin D synthase production in cultivated rat leptomeningeal cells

J Cereb Blood Flow Metab. 2004 Apr;24(4):409-18. doi: 10.1097/00004647-200404000-00006.


Although the interleukin (IL)-1 receptor is densely distributed in the leptomeninges constituting the blood/cerebrospinal fluid barrier, its physiologic significance has remained unclear. In the present study, we show that in cultured leptomeningeal cells, IL-1beta, tumor necrosis factors, or lipopolysaccharide causes a prominent increase in the synthesis and release of prostaglandin (PG) D synthase, which catalyzes the final step in the biosynthesis of PGD2. Although significant increases in the amount of PGD synthase were also observed with cells exposed to somatostatin, thrombin, or ciliary neurotrophic factor, these were much smaller than were those induced by the proinflammatory cytokines. Other agents tested including IGF-I had no effect upon the enzyme levels in the culture media. Furthermore, we found that the increased secretion of PGD synthase by IL-1beta was completely inhibited by 10(-7) M PGE2. The same dose of PGD2 or 15-deoxy-Delta(12-14)PGJ2 had no effect upon the IL-1beta action. In addition, PGE2 increased the level of fibronectin and eliminated the expression of zonula occludentes-1, a tight junction-associated protein from cultured cells, effects likely reflecting a loss of barrier integrity. These results demonstrate the importance of inflammatory stimuli as a physiologic regulator of the leptomeningeal cell function.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blotting, Western
  • Cells, Cultured
  • Dinoprostone / pharmacology*
  • Dose-Response Relationship, Drug
  • Fibronectins / metabolism
  • Interleukin-1 / pharmacology*
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / biosynthesis*
  • Lipocalins
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins / biosynthesis
  • Meninges / cytology
  • Meninges / drug effects*
  • Meninges / enzymology
  • NF-kappa B / metabolism
  • Phosphoproteins / biosynthesis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology
  • Zonula Occludens-1 Protein


  • Fibronectins
  • Interleukin-1
  • Lipocalins
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-kappa B
  • Phosphoproteins
  • RNA, Messenger
  • Tjp1 protein, rat
  • Tumor Necrosis Factor-alpha
  • Zonula Occludens-1 Protein
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase
  • Dinoprostone