Regulation of type V phospholipase A2 expression and function by proinflammatory stimuli

Eur J Biochem. 1999 Aug;263(3):826-35. doi: 10.1046/j.1432-1327.1999.00565.x.


Types IIA and V secretory phospholipase A2 (sPLA2) are structurally related to each other and their genes are tightly linked to the same chromosome locus. An emerging body of evidence suggests that sPLA2-IIA plays an augmentative role in long-term prostaglandin (PG) generation in cells activated by proinflammatory stimuli; however, the mechanism underlying the functional regulation of sPLA2-V remains largely unknown. Here we show that sPLA2-V is more widely expressed than sPLA2-IIA in the mouse, in which its expression is elevated by proinflammatory stimuli such as lipopolysaccharide. In contrast, proinflammatory stimuli induced sPLA2-IIA in marked preference to sPLA2-V in the rat. Cotransfection of sPLA2-V with cyclooxygenase (COX)-2, but not with COX-1, into human embryonic kidney 293 cells dramatically increased the interleukin-1-dependent PGE2 generation occurring over a 24 h of culture period. Rat mastocytoma RBL-2H3 cells overexpressing sPLA2-V exhibited increased IgE-dependent PGD2 generation and accelerated beta-hexosaminidase exocytosis. These results suggest that sPLA2-V acts as a regulator of inflammation-associated cellular responses. This possible compensation of sPLA2-V for sPLA2-IIA in many, if not all, tissues may also explain why some mouse strains with natural disruption of the sPLA2-IIA gene exhibit few abnormalities during their life-spans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Line
  • Dinoprostone / metabolism
  • Exocytosis
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology*
  • Heparin / pharmacology
  • Humans
  • Inflammation
  • Interleukin-1 / pharmacology
  • Isoenzymes
  • Kidney
  • Lipopolysaccharides / pharmacology*
  • Mast Cells / enzymology
  • Mast-Cell Sarcoma
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phospholipases A / biosynthesis
  • Phospholipases A / genetics*
  • Phospholipases A2
  • Prostaglandin D2 / metabolism
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / biosynthesis
  • Transfection
  • Tumor Cells, Cultured
  • beta-N-Acetylhexosaminidases / metabolism


  • Interleukin-1
  • Isoenzymes
  • Lipopolysaccharides
  • Recombinant Proteins
  • Heparin
  • Phospholipases A
  • Phospholipases A2
  • beta-N-Acetylhexosaminidases
  • Dinoprostone
  • Prostaglandin D2