Akiko Uehara

..The host defence system against P. gingivalis may be triggered through the activation of PARs by gingipains and augmented by PAMPs from this pathogen via TLRs or NOD1/2...

..These results suggest that gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation...

..These findings indicate that, in innate immune responses to invading microbes, a combination of signaling through TLRs and NODs leads to the synergistic activation of antibacterial responses in the oral epithelium...

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..These results suggest that Rgps activated human gingival fibroblasts to secrete HGF in the inflamed sites and the mechanism(s) involved may actively participate in both inflammatory and reparative processes in periodontal diseases...

..These findings indicate that TLR and NOD in various epithelial cells are functional receptors that induce anti-bacterial responses in general without being accompanied by inflammatory responses...

..The results suggest that anti-PR3 Abs (PR3 ANCA) prime human epithelial cells to produce cytokines upon stimulation with various PAMPs, and these mechanisms may be involved in severe chronic inflammation in WG...

..These findings suggest that neutrophil serine proteinases have equal ability to activate human nonepithelial cells through PAR-2 to produce inflammatory cytokines and may control a number of inflammatory processes such as periodontitis...

..These results suggest that endogenous membrane-bound IL-15 sustains recruitment of IL-2Rbeta and gammac through activation of NF-kappaB in HGF...

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..In addition, saliva contains abundant bio-active CD14 from salivary glands in a soluble form, although LPS-binding protein was below detectable levels, suggesting that saliva CD14 is important for the maintenance of oral health...

..These findings suggest that neutrophil PR3 activates oral epithelial cells through G protein-coupled PAR-2 and actively participates in the process of inflammation such as periodontitis...

..Our results should help clarify how the intestinal immune system is modulated by low-molecular weight peptidoglycan fragments through NOD1...

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..These findings strongly suggested that a polymer-type water-soluble PGN fragment, SEPS, exhibits both TLR2-and NOD2-agonistic activities, which induced the synergistic activation of human monocytic cells...

..These results suggested that saliva CD14 is important for the maintenance of oral health and possibly intestinal homeostasis...

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..The detailed analysis of Sn binding pockets revealed the molecular basis of inhibitory affinity and provided insight into the structure-activity relationship...

..Degradation of integrin beta1 was inhibited only in the presence of z-VAD-FMK. These results further clarify the role P. gingivalis plays in tissue destruction occurring in the periodontal pocket...

..gingivalis outer membrane. Moreover, our results indicate that the immunoglobulin-like subdomain is indispensable for proper folding and expression of the gingipains...

..Porphyromonas gingivalis is a causative bacterium of adult periodontitis. However, there is no drug specific for P. gingivalis and for its virulence factor...

..This result may have a wider implication in a novel secretory pathway in distinct members of the Cytophaga-Flavobacterium-Bacteroidetes phylum...

..W. Smalley, M.F. Thomas, A.J. Birss, R. Withnall, J. Silver, Biochem. J. 379 (2004) 833-840.] of the requirement for a combination of both R- and K-gingipains for pigment production from oxyhaemoglobin by P. gingivalis...

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..gingivalis...

..Obtained from these procedures, the gingipains are stable and can be stored at -80 degrees C for years without loss of activity...

..Haem-free globin was rapidly degraded by K-gingipain. These data emphasise the need for haemoglobin oxidation which encourages haem dissociation and makes the haem-free globin susceptible to proteolytic attack...

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..At later stages of infection the concentration of proteases is high enough to destroy complement factors and thus render the bacteria resistant to the bactericidal activity of complement...

..This new RgpB activity suggests a possible link between periodontitis and pulp inflammation, which may be modulated by neuropeptides released in the lesion...

..Taken together, these results indicate that gingipains from P. gingivalis can alter cell adhesion molecules and induce endothelial cell death, which could have implications for the pathogenicity of this organism...

..This hypothetical scenario is a reasonable explanation for the occurrence of many forms of gingipains...

..Collectively, these results indicate that kgp , rgpA and hmuR gene transcription is coordinately regulated and may facilitate greater efficiency of heme utilization in P. gingivalis ...

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..Each step in activation requires the previous step, and an affinity probe reveals that incremental activity enhancements are achieved in a stepwise manner...

..gingivalis. Gingipains are potent virulence factors of P. gingivalis, and in many regards their pathogenic activities constitute new mechanisms of bacterial virulence...

..Thus, gingipains are able not only to cleave soluble TNF-alpha but also to destroy the membrane form of the cytokine, which may additionally dysregulate the cytokine network...

..gingivalis the inflammatory reactions dependent on IL-6 could be severely hindered contributing to both tissue damage and periodontopathogen survival...

..Together these results indicate that RNR class III is an important virulence factor for the establishment of septic arthritis...

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..Possibly enters the majority of bacteria a metabolically dormant steady state at high bacterial loads...

..These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain...

..S. aureus persists inside macrophages for several days without affecting the viability of these mobile cells which may serve as vehicles for the dissemination of infection...

..Unexpectedly for a cysteine protease inhibitor, staphostatin B is not significantly similar to cystatins...

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..Mutations in this residue lead to a loss of affinity of the inhibitor for protease and convert the inhibitor into a substrate...

..In summary, we have discovered a new series of effective inhibitors for the gingipains and found a novel way to increase inhibitor potency with the HRgpA and RgpB gingipains using zinc...

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..The structure of this first molecular determinant of methicillin resistance in complex with its target DNA provides insights into its regulatory mechanism and paves the way for new antimicrobial strategies against MRSA...

..Aza-Lys and aza-Orn derivatives were potent inhibitors of gingipain K and clostripain. Aza-peptide Michael acceptors showed no cross reactivity toward papain, cathepsin B, and calpain...

..aureus virulence and bacterial shock. Therefore, staphopain-specific inhibitors and kinin-receptor antagonists could be used to treat this disease...

..This apparently represents a novel system that bacteria use to control the intracellular activity of their proteases...

..Taken together, the ability of NE and CG to modulate levels of membrane and soluble forms of TNFalpha may contribute to the proinflammatory activity of neutrophils...

..Seemingly, some of these proteins may play a role in protein secretion; hence, their proteolytic inactivation by SspB has pleiotropic effects on the SspC-deficient mutant...

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..gingivalis by exacerbating local and systemic inflammation, thereby contributing to the morbidity and mortality associated with infection...

..Interestingly, aeruginolysin bearing two additional residues at the N-terminus (Leu-Lys-aeruginolysin) in the absence of calcium degraded both IL-6 and IL-8-72 far more efficiently than the shorter form of the enzyme...

..These results demonstrate that AP stimulates shedding of cell-surface TNFR1, resulting in an increase in sTNFR1. Consequently, these events decrease the cells' ability to stimulate RANTES gene expression and secretion through TNFR1...

..In a modeled complex of prostaphopain B with staphostatin B, clashes occur both inside and outside the active site cleft, but involve mostly poorly ordered regions of the protein that may be mobile...

..The tight coevolution is likely the result of the known deleterious effects of uncontrolled staphopain action...

..The difference in the susceptibility of individual inhibitors to proteolytic cleavage at the reactive site suggests subtle variations in the mechanism of interaction with cysteine proteases...

..SspB may help direct the recruitment of specialized host cells, including immunoregulatory pDC and/or macrophages, contributing to the ability of S. aureus to elicit and maintain a chronic inflammatory state...

..Results presented for the specificity of staphopains when interacting with cystatins as natural protein substrates could aid in the development of therapeutic agents directed toward these proteolytic virulence factors...

..This enzyme, with elastinolytic properties, as well as the ability to cleave alpha1PI, fibrinogen and fibronectin, may possibly contribute to the invasiveness and pathogenic potential of S. epidermidis...

..Porphyromonas gingivalis contains a superoxide dismutase but lacks catalase and haem peroxidases. We therefore suggest that rubrerythrin provides oxidative stress protection via catalytic reduction of intracellular hydrogen peroxide...