Study on the action by PAF on IL-1 modulation in alveolar macrophages: Involvement of endogenous arachidonate metabolites and intracellular Ca++ mobilization.
- Author:
Jihee LEE
1
;
Won Ki KIM
;
Jong Sik HAH
Author Information
1. Department of Physiology, College of Medicine, Ewha Womans University, Seoul 158-056, Korea.
- Publication Type:Original Article
- Keywords:
PAF;
IL-1;
Alveolar Macrophages;
Lipoxygenase inhibitors;
Cyclooxygenase inhibitors;
Leukotriene B4;
Prostaglandin E2;
Intracellular Ca++ mobilization
- MeSH:
Animals;
Arachidonate 5-Lipoxygenase;
Calcium;
Cyclooxygenase Inhibitors;
Dinoprostone;
Fura-2;
Ibuprofen;
Indomethacin;
Inhibitory Concentration 50;
Interleukin-1*;
Leukotriene B4;
Lipoxygenase Inhibitors;
Macrophages, Alveolar*;
Masoprocol;
Prostaglandin-Endoperoxide Synthases;
Rats;
Thymocytes
- From:The Korean Journal of Physiology and Pharmacology
1998;2(2):241-249
- CountryRepublic of Korea
- Language:English
-
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 24 h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with IC50 of 2 micrometer and 5 micrometer, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at 1 micrometer and 5 micrometer, 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 PAFstimulated 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 10-8M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium 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-lpoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.
