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 language | English |
|---|---|
| Pages (from-to) | 241-249 |
| Number of pages | 9 |
| Journal | Korean Journal of Physiology and Pharmacology |
| Volume | 2 |
| Issue number | 2 |
| Publication status | Published - 1998 Jan 1 |
| Externally published | Yes |
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Keywords
- Alveolar macrophages
- Cyclooxygenase inhibitors
- IL-1
- Intracellular Ca mobilization
- Leukotriene B
- Lipoxygenase inhibitors
- PAF
- Prostaglandin E
ASJC Scopus subject areas
- Physiology
- Pharmacology
Cite this
Study on the action of PAF on IL-1 modulation in alveolar macrophages : Involvement of endogenous arachidonate metabolites and intracellular Ca++ mobilization. / Lee, J.; Kim, Won-Ki; Hah, J. S.
In: Korean Journal of Physiology and Pharmacology, Vol. 2, No. 2, 01.01.1998, p. 241-249.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Study on the action of PAF on IL-1 modulation in alveolar macrophages
T2 - Involvement of endogenous arachidonate metabolites and intracellular Ca++ mobilization
AU - Lee, J.
AU - Kim, Won-Ki
AU - Hah, J. S.
PY - 1998/1/1
Y1 - 1998/1/1
N2 - 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.
AB - 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.
KW - Alveolar macrophages
KW - Cyclooxygenase inhibitors
KW - IL-1
KW - Intracellular Ca mobilization
KW - Leukotriene B
KW - Lipoxygenase inhibitors
KW - PAF
KW - Prostaglandin E
UR - http://www.scopus.com/inward/record.url?scp=0031781060&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031781060&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0031781060
VL - 2
SP - 241
EP - 249
JO - Korean Journal of Physiology and Pharmacology
JF - Korean Journal of Physiology and Pharmacology
SN - 1226-4512
IS - 2
ER -