Role of Cytosolic Phospholipase A2 in Cytokine-Stimulated Prostaglandin Release by Human Gallbladder Cells

Erik M. Grossmann, Walter E. Longo, John E. Mazuski, Ninder Panesar, Donald L. Kaminski

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Eicosanoids are involved in gallbladder inflammation, epithelial water transport, and mucous secretion. Phospholipase A2 enzymes liberate arachidonic acid from membrane phospholipids for the synthesis of eicosanoids. The purpose of this study was to determine the effect of selective cytoplasmic and secretory phospholipase A2 inhibitors on basal and stimulated arachidonic acid and prostaglandin F2 release in gallbladder cells. Western immunoblotting was employed to evaluate both cytosolic and secretory phospholipase A2 enzymes in human gallbladder cells. Cells were incubated for 22 hours with 1H-labeled arachidonic acid. Arachidonic acid and prostaglandin F2 release was then measured in the supernate after 2 hours of exposure to human interleukin-1β, alone or after pretreatment tor 1 hour with the inhibitors. Unstimulated gallbladder cells express both 85 kDa cytosolic and 14 kDa secretoty phospholipase A2. The 85 kDa phospholipase A2 was induced by interleukin-1β, whereas there was no apparent change in secretory phospholipase A2 enzyme concentrations. Both the secretory phospholipase A2 inhibitor p-bromophenylacyl bromide and the cytosolic phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone decreased basal and interleukin-1β-stimulated arachidonic acid release. In contrast, only inhibition of cytosolic phospholipase A2 led to a decrease in interleukin-1β-stimulated prostaglandin E2 release. Basal and interleukin-1β-stimulated arachidonic acid release appears to be the result of the activity of both cytosolic and secretory phospholipase A2. Interleukin-1β-stimulated prostaglandin E2 release appears to he dependent on the activity of cytosolic phospholipase A2.

Original languageEnglish
Pages (from-to)193-200
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume4
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Gallbladder
  • Interleukin-1β
  • Phospholipase A
  • Prostaglandins

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