Abstract

Recently, under large-scale screening experiments, we found that sphondin, a furanocoumarin derivative isolated from Heracleum laciniatum, possessed an inhibitory effect on IL-1β-induced increase in the level of COX-2 protein and PGE2 release in A549 cells. Accordingly, we examined in the present study the action mechanism of sphondin on the inhibition of IL-1β-induced COX-2 protein expression and PGE2 release in a human pulmonary epithelial cell line (A549). Pretreatment of cells with sphondin (10-50 μM) concentration-dependently attenuated IL-1β-induced COX-2 protein expression and PGE2 release. The IL-1β-induced increase in COX-2 mRNA expression was also attenuated by sphondin (50 μM). The selective COX-2 inhibitor, NS-398 (0.01-1 μM), inhibited the activity of the COX-2 enzyme in a concentration-dependent manner, while sphondin (10-50 μM) had no effect. Sphondin (50 μM) did not affect the IL-1β-induced activations of p44/42 MAPK, p38 MAPK, and JNK. Treatment of cells with sphondin (50 μM) or the NF-κB inhibitor, PDTC (50 μM) partially inhibited IL-1β-induced degradation of IκB-α in the cytosol and translocation of p65 NF-κB from the cytosol to the nucleus. Furthermore, IL-1β-induced NF-κB-specific DNA-protein complex formation in the nucleus was partially inhibited by sphondin (50 μM) or PDTC (50 μM). Taken together, we demonstrate that sphondin inhibits IL-1β-induced PGE2 release in A549 cells; this inhibition is mediated by suppressing of COX-2 expression, rather than by inhibiting COX-2 enzyme activity. The inhibitory mechanism of sphondin on IL-1β-induced COX-2 expression may be, at least in part, through suppression of NF-κB activity. We conclude that sphondin may have the therapeutic potential as an anti-inflammatory drug on airway inflammation.

Original languageEnglish
Pages (from-to)199-213
Number of pages15
JournalLife Sciences
Volume72
Issue number2
DOIs
Publication statusPublished - Nov 29 2002

Fingerprint

Heracleum
Cyclooxygenase 2
Interleukin-1
Epithelial Cells
Lung
Dinoprostone
Cytosol
Proteins
sphondin
Cells
Mitogen-Activated Protein Kinase 3
Cyclooxygenase 2 Inhibitors
Enzyme activity
p38 Mitogen-Activated Protein Kinases
Enzymes

Keywords

  • Cyclooxygenase-2
  • Heracleum laciniatum
  • Nuclear factor-κB
  • Sphondin

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{4ee238da2c2442cfb0eb85e7785e8807,
title = "Effects of sphondin, isolated from Heracleum laciniatum, on IL-1β-induced cyclooxygenase-2 expression in human pulmonary epithelial cells",
abstract = "Recently, under large-scale screening experiments, we found that sphondin, a furanocoumarin derivative isolated from Heracleum laciniatum, possessed an inhibitory effect on IL-1β-induced increase in the level of COX-2 protein and PGE2 release in A549 cells. Accordingly, we examined in the present study the action mechanism of sphondin on the inhibition of IL-1β-induced COX-2 protein expression and PGE2 release in a human pulmonary epithelial cell line (A549). Pretreatment of cells with sphondin (10-50 μM) concentration-dependently attenuated IL-1β-induced COX-2 protein expression and PGE2 release. The IL-1β-induced increase in COX-2 mRNA expression was also attenuated by sphondin (50 μM). The selective COX-2 inhibitor, NS-398 (0.01-1 μM), inhibited the activity of the COX-2 enzyme in a concentration-dependent manner, while sphondin (10-50 μM) had no effect. Sphondin (50 μM) did not affect the IL-1β-induced activations of p44/42 MAPK, p38 MAPK, and JNK. Treatment of cells with sphondin (50 μM) or the NF-κB inhibitor, PDTC (50 μM) partially inhibited IL-1β-induced degradation of IκB-α in the cytosol and translocation of p65 NF-κB from the cytosol to the nucleus. Furthermore, IL-1β-induced NF-κB-specific DNA-protein complex formation in the nucleus was partially inhibited by sphondin (50 μM) or PDTC (50 μM). Taken together, we demonstrate that sphondin inhibits IL-1β-induced PGE2 release in A549 cells; this inhibition is mediated by suppressing of COX-2 expression, rather than by inhibiting COX-2 enzyme activity. The inhibitory mechanism of sphondin on IL-1β-induced COX-2 expression may be, at least in part, through suppression of NF-κB activity. We conclude that sphondin may have the therapeutic potential as an anti-inflammatory drug on airway inflammation.",
keywords = "Cyclooxygenase-2, Heracleum laciniatum, Nuclear factor-κB, Sphondin",
author = "Ling-Ling Yang and Liang, {Yu Chih} and Chang, {Chia Wen} and Lee, {Wen Sen} and Kuo, {Chen Tzu} and Wang, {Ching Chiung} and Lee, {Horng Mo} and Lin, {Chien Huang}",
year = "2002",
month = "11",
day = "29",
doi = "10.1016/S0024-3205(02)02173-2",
language = "English",
volume = "72",
pages = "199--213",
journal = "Life Sciences",
issn = "0024-3205",
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TY - JOUR

T1 - Effects of sphondin, isolated from Heracleum laciniatum, on IL-1β-induced cyclooxygenase-2 expression in human pulmonary epithelial cells

AU - Yang, Ling-Ling

AU - Liang, Yu Chih

AU - Chang, Chia Wen

AU - Lee, Wen Sen

AU - Kuo, Chen Tzu

AU - Wang, Ching Chiung

AU - Lee, Horng Mo

AU - Lin, Chien Huang

PY - 2002/11/29

Y1 - 2002/11/29

N2 - Recently, under large-scale screening experiments, we found that sphondin, a furanocoumarin derivative isolated from Heracleum laciniatum, possessed an inhibitory effect on IL-1β-induced increase in the level of COX-2 protein and PGE2 release in A549 cells. Accordingly, we examined in the present study the action mechanism of sphondin on the inhibition of IL-1β-induced COX-2 protein expression and PGE2 release in a human pulmonary epithelial cell line (A549). Pretreatment of cells with sphondin (10-50 μM) concentration-dependently attenuated IL-1β-induced COX-2 protein expression and PGE2 release. The IL-1β-induced increase in COX-2 mRNA expression was also attenuated by sphondin (50 μM). The selective COX-2 inhibitor, NS-398 (0.01-1 μM), inhibited the activity of the COX-2 enzyme in a concentration-dependent manner, while sphondin (10-50 μM) had no effect. Sphondin (50 μM) did not affect the IL-1β-induced activations of p44/42 MAPK, p38 MAPK, and JNK. Treatment of cells with sphondin (50 μM) or the NF-κB inhibitor, PDTC (50 μM) partially inhibited IL-1β-induced degradation of IκB-α in the cytosol and translocation of p65 NF-κB from the cytosol to the nucleus. Furthermore, IL-1β-induced NF-κB-specific DNA-protein complex formation in the nucleus was partially inhibited by sphondin (50 μM) or PDTC (50 μM). Taken together, we demonstrate that sphondin inhibits IL-1β-induced PGE2 release in A549 cells; this inhibition is mediated by suppressing of COX-2 expression, rather than by inhibiting COX-2 enzyme activity. The inhibitory mechanism of sphondin on IL-1β-induced COX-2 expression may be, at least in part, through suppression of NF-κB activity. We conclude that sphondin may have the therapeutic potential as an anti-inflammatory drug on airway inflammation.

AB - Recently, under large-scale screening experiments, we found that sphondin, a furanocoumarin derivative isolated from Heracleum laciniatum, possessed an inhibitory effect on IL-1β-induced increase in the level of COX-2 protein and PGE2 release in A549 cells. Accordingly, we examined in the present study the action mechanism of sphondin on the inhibition of IL-1β-induced COX-2 protein expression and PGE2 release in a human pulmonary epithelial cell line (A549). Pretreatment of cells with sphondin (10-50 μM) concentration-dependently attenuated IL-1β-induced COX-2 protein expression and PGE2 release. The IL-1β-induced increase in COX-2 mRNA expression was also attenuated by sphondin (50 μM). The selective COX-2 inhibitor, NS-398 (0.01-1 μM), inhibited the activity of the COX-2 enzyme in a concentration-dependent manner, while sphondin (10-50 μM) had no effect. Sphondin (50 μM) did not affect the IL-1β-induced activations of p44/42 MAPK, p38 MAPK, and JNK. Treatment of cells with sphondin (50 μM) or the NF-κB inhibitor, PDTC (50 μM) partially inhibited IL-1β-induced degradation of IκB-α in the cytosol and translocation of p65 NF-κB from the cytosol to the nucleus. Furthermore, IL-1β-induced NF-κB-specific DNA-protein complex formation in the nucleus was partially inhibited by sphondin (50 μM) or PDTC (50 μM). Taken together, we demonstrate that sphondin inhibits IL-1β-induced PGE2 release in A549 cells; this inhibition is mediated by suppressing of COX-2 expression, rather than by inhibiting COX-2 enzyme activity. The inhibitory mechanism of sphondin on IL-1β-induced COX-2 expression may be, at least in part, through suppression of NF-κB activity. We conclude that sphondin may have the therapeutic potential as an anti-inflammatory drug on airway inflammation.

KW - Cyclooxygenase-2

KW - Heracleum laciniatum

KW - Nuclear factor-κB

KW - Sphondin

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DO - 10.1016/S0024-3205(02)02173-2

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JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

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