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

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology

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