Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 32, Issue 10, Pages 1770-1775Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.32.1770
Keywords
panduratin A; Porphyromonas gingivalis supernatant; c-Jun N-terminal kinase; activator protein-1; matrix metalloproteinase-9; human oral epidermoid cell
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Funding
- Brain Korea 21
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Porphyromonas gingivalis, a type of Gram-negative periodontopathogen, causes periodontal disease by activating intracellular signaling pathways that produce excessive inflammatory responses such as matrix metalloproteinases (MMPs). Recently, we reported that panduratin A, a chalcone compound isolated from Kaempferia pandurata ROXB., caused the decreased levels of MMP-9 secretion, protein, and gene expression in human oral epidermoid KB cells exposed to P gingivalis supernatant. In this study, we clarified if mitogen-activated protein kinase (MAPK) signaling mediated MMP-9 expression by examining the effect of specific MAPK inhibitors, i.e. U0126, SB203580, and SP600125, on P gingivalis supernatant-stimulated MMP-9 expression in KB cells. We next elucidated the molecular mechanism by which panduratin A attenuated signaling pathways involved in MMP-9 expression by performing gelatin zymography, Western blotting, reverse transcription-polymerase chain reaction, and promoter assays. Exposure of KB cells to P gingivalis supernatant up-regulated the expression of MMP-9 protein and gene, and activation of activator protein-1 (AP-1) element, MAPK phosphorylation (extracellular signal-related kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK)), and transcription factors (Elk1, c-Jun, and c-Fos). A JNK inhibitor (SP600125) significantly attenuated MMP-9 gene expression and AP-1 activity in KB cells in response to P gingivalis supernatant. Similar to SP600125, panduratin A was found to strongly suppress the level of phosphorylated JNK and block AP-1 activity in R gingivalis supernatant-stimulated KB cells. In summary, JNK and AP-1 are the major signaling for P gingivalis supernatant-stimulated MMP-9 expression in KB cells, and panduratin A markedly down-regulates MMP-9 expression through inhibition of these signaling.
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