Platelet-activating factor and endotoxin increase the enzyme activity and gene expression of type II phospholipase A2 in the rat intestine: Role of polymorphonuclear leukocytes

Xiao Di Tan, Hao Wang, Francis X. Gonzalez-Crussi, Hong Chang, Frank Gonzalez-Crussi, Wei Hsueh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Type II phospholipase A2 (PLA2-II) may regulate eicosanoid synthesis; is involved in various inflammatory processes, septic shock, and inflammatory bowel disease; and is up-regulated by LPS and inflammatory cytokines in vitro. We have previously shown that the platelet-activating factor (PAF)-induced intestinal injury is attenuated by peptido-leukotriene antagonists, suggesting a role of PLA2. The purpose of this study is to examine the regulation of intestinal PLA2-II by PAF and LPS. Using synthesized competitor RNA as competitor, we quantified PLA2-II transcripts by competitive reverse transcription-PCR. We found that PLA2-II gene is constitutively expressed in the rat ileum. PAF at a dose (1.5 μg/kg) below that causing intestinal injury rapidly up-regulated intestinal PLA2-II at both transcriptional and post-transcriptional levels, almost tripling its transcripts and significantly increasing enzyme activity in 30 min. LPS (5 mg/kg) also up-regulated PLA2-II. This effect could not be blocked by PAF antagonist. Depletion of circulating polymorphonuclear leukocytes (PMNs) abolished the effect of PAF on PLA2-II gene expression and enzyme activation. In contrast, PMN depletion prevented LPS-induced PLA2-II enzyme activity but enhanced the gene expression. We conclude that: 1) both PAF and LPS induce gene transcription and enzyme activation of PLA2-II in the small intestine; 2) PAF up-regulates PLA2-II via PMN activation; 3) LPS effect is independent of endogenous PAF formation; and 4) different pathways exist for PAF and LPS in the regulation of intestinal PLA2-II gene expression in vivo.

Original languageEnglish (US)
Pages (from-to)2985-2990
Number of pages6
JournalJournal of Immunology
Volume156
Issue number8
StatePublished - Apr 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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