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 language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - Apr 15 1996|
ASJC Scopus subject areas
- Immunology and Allergy