Inhibitory effect of panduratin A on c-Jun N-terminal kinase and activator protein-1 signaling involved in Porphyromonas gingivalis supernatant-stimulated matrix metalloproteinase-9 expression in human oral epidermoid cells.
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 P. 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.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seodaemun-gu, Seoul 120-749, Korea.
Yanti
Myoungsu
M
Lee
Daeyoung
D
Kim
Jae-Kwan
JK
Hwang
D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D007624:KB Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009055:Mouth; D010518:Periodontitis / Q000382:microbiology; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000472:pathogenicity; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D027343:Rhizome; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D030521:Zingiberaceae / Q000737:chemistry*
D047188:Chalcones; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C482884:panduratin A; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9