Effects of sphondin, isolated from Heracleum laciniatum, on IL-1beta-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-1beta-induced increase in the level of COX-2 protein and PGE(2) release in A549 cells. Accordingly, we examined in the present study the action mechanism of sphondin on the inhibition of IL-1beta-induced COX-2 protein expression and PGE(2) release in a human pulmonary epithelial cell line (A549). Pretreatment of cells with sphondin (10-50 microM) concentration-dependently attenuated IL-1beta-induced COX-2 protein expression and PGE(2) release. The IL-1beta-induced increase in COX-2 mRNA expression was also attenuated by sphondin (50 microM). The selective COX-2 inhibitor, NS-398 (0.01-1 microM), inhibited the activity of the COX-2 enzyme in a concentration-dependent manner, while sphondin (10-50 microM) had no effect. Sphondin (50 microM) did not affect the IL-1beta-induced activations of p44/42 MAPK, p38 MAPK, and JNK. Treatment of cells with sphondin (50 microM) or the NF-kappaB inhibitor, PDTC (50 microM) partially inhibited IL-1beta-induced degradation of IkappaB-alpha in the cytosol and translocation of p65 NF-kappaB from the cytosol to the nucleus. Furthermore, IL-1beta-induced NF-kappaB-specific DNA-protein complex formation in the nucleus was partially inhibited by sphondin (50 microM) or PDTC (50 microM). Taken together, we demonstrate that sphondin inhibits IL-1beta-induced PGE(2) 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-1beta-induced COX-2 expression may be, at least in part, through suppression of NF-kappaB activity. We conclude that sphondin may have the therapeutic potential as an anti-inflammatory drug on airway inflammation.

• Authors: Ling Ling Yang, Yu Chih Liang, Chia Wen Chang, Wen Sen Lee, Chen Tzu Kuo, Ching Chiung Wang, Horng Mo Lee, Chien Huang Lin
• Journal: Life sciences (Life Sci) Vol. 72 Issue 2 Pg. 199-213 (Nov 29 2002) ISSN: 0024-3205 [Print] Netherlands
• PMID: 12417253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• Isoenzymes
• Membrane Proteins
• NF-kappa B
• sphondin
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinase 8
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Dinoprostone
• Methoxsalen

Topics

• Blotting, Northern
• Blotting, Western
• Cell Line
• Cell Nucleus (chemistry)
• Cell Survival (drug effects)
• Cyclooxygenase 2
• Dinoprostone (metabolism)
• Electrophoresis
• Enzyme Activation (drug effects)
• Epithelial Cells (drug effects, enzymology)
• Heracleum (chemistry)
• Humans
• Interleukin-1 (pharmacology)
• Isoenzymes (biosynthesis)
• Lung (cytology, drug effects, enzymology)
• Membrane Proteins
• Methoxsalen (analogs & derivatives, pharmacology)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinase 8
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (drug effects)
• Prostaglandin-Endoperoxide Synthases (biosynthesis)
• p38 Mitogen-Activated Protein Kinases