title: Early and preferential induction of IL-1 receptor-associated kinase-M in THP-1 cells by LPS derived from Porphyromonas gingivalis.
abstract: LPS of Porphyromonas gingivalis (P. gingivalis) is suggested to be a virulence factor in periodontitis, stimulating host cells to produce proinflammatory mediators. However, P. gingivalis LPS has been reported to show lower biological activity compared with Escherichia coli (E. coli) LPS. Although differences in the chemical structure of lipid A and the receptor conferring LPS signaling are thought to account for these characteristics, the precise reason is unknown. Here, we demonstrate that P. gingivalis LPS up-regulates IL-1R-associated kinase (IRAK)-M, a negative regulator 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-stimulated cells. Degradation of IRAK-1 was more obvious in E. coli LPS-stimulated macrophages than the cells stimulated with P. gingivalis LPS, suggesting that P. gingivalis LPS-induced IRAK-M suppressed 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 periodontal tissue by serving as an escape mechanism from immune surveillance.
authors.affiliation: Laboratory of Periodontology and Immunology, Department of Oral Health and Welfare, Faculty of Dentistry, Niigata University, 5274 Gakkocho 2-ban-cho, Chu-o-ku, Niigata, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Domon
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honda
authors.forename: Taro
authors.initials: T
authors.lastname: Oda
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects*; D004926:Escherichia coli; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D016966:Porphyromonas gingivalis; D034741:RNA, Small Interfering; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases