Macelignan suppresses Porphyromonas gingivalis supernatant-stimulated urokinase-type plasminogen activator expression via signal transduction in human KB oral cells

Macelignan, a bioactive compound isolated from Myristica fragrans Houtt. or nutmeg, has been reported for its anti-cariogenic and anti-biofilm activities for dental plaque control [1,2]. However, its efficacy to block the expression of urokinase-type plasminogen activator (uPA), a serine protease that is expressed in various inflamed and normal healing cell types in response to cytokines and bacterial products, for periodontal inflammation treatment has not been investigated. This study was aimed to examine whether macelignan suppressed Porphyromonas gingivalis supernatant-stimulated uPA expression through regulation of mitogen-activated protein kinase (MAPK) and activating protein (AP)-1 signalings in human KB oral cells by performing casein zymography, reverse transcription-PCR, Western blotting, and reporter gene assays. The main caseinolytic band secreted from the cells was found to be migrated at 54 kDa and represented uPA. Macelignan dose-dependently inhibited the expression of uPA activity, protein, and gene in KB cells in response to P. gingivalis supernatant. In accordance with these findings, macelignan effectively decreased phosphorylation of p38 and c-jun N terminal kinase (JNK) in P. gingivalis supernatant-stimulated KB cells. The levels of c-jun phosphorylation and c-fos expression, which composed of AP-1 transcription factor for uPA gene expression, were also reduced by macelignan in KB cells exposed to P. gingivalis supernatant. In linear with these results, macelignan was found to block P. gingivalis supernatant-stimulated AP-1 activity in KB cells. These results suggest that macelignan decreased P. gingivalis supernatant-stimulated uPA expression by blocking AP-1 activity which may be facilitated by inhibiting phosphorylation of p38 and JNK in KB cells.

References: [1] Chung, J.Y. et al. (2006) Phytomedicine 13:261–266.

[2] Yanti et al. (2008) Phytother. Res. 22:308–312.