Study on the action of PAF on IL-1 modulation in alveolar macrophages: Involvement of endogenous arachidonate metabolites and intracellular Ca++ mobilization

J. Lee, Won-Ki Kim, J. S. Hah

Research output: Contribution to journalArticle

Abstract

Platelet-activating factor (PAF) enhanced interleukin-1 (IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide (LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxyenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with IC50 of 2 μM and 5 μM, respectively. In contrast, the inhibition of cyclooxygenae pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at 1 μM and 5 μM, respectively. In addition, leukotriene B4 and prostaglandin E2 production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF-stimulated leukotriene B4 and prostaglandin E2 production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium- sensitive dye fura-2 at the single cell level. PAF at any dose between 10- 16 and 10-8 M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24, and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalKorean Journal of Physiology and Pharmacology
Volume2
Issue number2
Publication statusPublished - 1998 Jan 1
Externally publishedYes

Keywords

  • Alveolar macrophages
  • Cyclooxygenase inhibitors
  • IL-1
  • Intracellular Ca mobilization
  • Leukotriene B
  • Lipoxygenase inhibitors
  • PAF
  • Prostaglandin E

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

Fingerprint Dive into the research topics of 'Study on the action of PAF on IL-1 modulation in alveolar macrophages: Involvement of endogenous arachidonate metabolites and intracellular Ca<sup>++</sup> mobilization'. Together they form a unique fingerprint.

  • Cite this