Porphyromonas gingivalis

gingivalis) is suggested to be a virulence factor in periodontitis, stimulating host cells to produce proinflammatory mediators. However, P. gingiva-lis LPS has been reported to show lower biological activity compared with Escherichia coli (E. coli) LPS. Although differences in the chemical struc-ture of lipid A and the receptor conferring LPS signaling are thought to account for these charac-teristics, the precise reason is unknown. Here, we demonstrate that P. gingivalis LPS up-regulates IL-1R-associated kinase (IRAK)-M, a negative reg-ulator of the TLR signaling pathway, in a THP-1-derived macrophage more robustly than E. coli LPS. Although down-regulation of IRAK-M by small interfering (si)RNA augmented transcription and translation of TNF-, IL-6, and IL-12 p40 in LPS-stimulated macrophages, the effect of siRNA was more prominent in P. gingivalis LPS-stimu-lated cells. Degradation of IRAK-1 was more ob-vious in E. coli LPS-stimulated macrophages than the cells stimulated with P. gingivalis LPS, suggest-ing that P. gingivalis LPS-induced IRAK-M sup-pressed dissociation of IRAK-1 from the receptor complex, resulting in escape from subsequent degradation. This activity may be involved in the chronic infection of this bacterium in periodon-tal tissue by serving as an escape mechanism from immune surveillance. J. Leukoc. Biol. 83