J Med Microbiol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishida, I.
Right arrow Articles by Shimamura, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishida, I.
Right arrow Articles by Shimamura, T.
Agricola
Right arrow Articles by Ishida, I.
Right arrow Articles by Shimamura, T.
J Med Microbiol 56 (2007), 1042-1046; DOI: 10.1099/jmm.0.47029-0
© 2007 Society for General Microbiology
ISSN 1473-5644

Epigallocatechin gallate suppresses expression of receptor activator of NF-{kappa}B ligand (RANKL) in Staphylococcus aureus infection in osteoblast-like NRG cells

Ikuo Ishida1,2, Chikara Kohda1, Yoko Yanagawa1, Hideyo Miyaoka2 and Tadakatsu Shimamura1

1 Department of Microbiology and Immunology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

2 Department of Orthopedic Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Correspondence
Ikuo Ishida
ikuo-i29{at}sea.plala.or.jp

Received 26 October 2006
Accepted 25 March 2007

Catechin, a constituent of tea, possesses various bioactivities. In particular, the most abundant catechin in tea is epigallocatechin gallate (EGCg), which has an anti-inflammatory effect. In the present study, the usability of EGCg for osteomyelitis treatment was examined. Osteomyelitis is a difficult disease to cure, partly due to bone lysis caused by infected osteoblasts. Since bone lysis is promoted by proinflammatory cytokines and the receptor activator of NF-{kappa}B ligand (RANKL), osteoblasts were infected with Staphylococcus aureus and the effect of EGCg on the production of cytokines was examined. It was found that the production of interleukin 6 and RANKL was suppressed in the osteoblasts treated with EGCg, which indicated an inflammation suppression effect of EGCg in osteomyelitis treatment.

Abbreviations: EGCg, epigallocatechin gallate; IL, interleukin; RANKL, receptor activator of NF-{kappa}B ligand; TLR, Toll-like receptor; TNF, tumour necrosis factor.


   INTRODUCTION
TOP
 INTRODUCTION
METHODS
 RESULTS AND DISCUSSION
 REFERENCES
 
Osteomyelitis causes progressive inflammatory destruction of bone (Sax & Lew, 1999). The number of infectious diseases of bones and joints has increased because of new drug-resistant bacteria, the development of artificial joint replacement techniques, and an increase in the number of compromised patients and elderly people (Morris et al., 2006). Due to its intractability, recurrence and chronicity of osteomyelitis are a major problem. Chronic osteomyelitis is intractable because sequestrum, pus or diseased granulation tissue inside bone marrow lesions causes poor blood circulation in the diseased part and hence lowers the effective concentration of antibiotics against pathogens. Another obstacle to treatment is inflammatory bone resorption by infected osteoblasts (Wright & Friedland, 2004). Tumour necrosis factor alpha (TNF-{alpha}) acts on marrow-derived macrophages to promote the induction of differentiation to osteoclast cells (Kobayashi et al., 2000; Azuma et al., 2000), and interleukin 1 (IL-1) and the receptor activator of NF-{kappa}B ligand (RANKL) acts on mature osteoclast cells to induce bone resorption activity (Jimi et al., 1999). If IL-1 or IL-6 affects osteoblasts, the expression of RANKL, an osteoclast differentiation factor, is induced causing bone resorption (Suda et al., 1999; Yasuda et al., 1998). In addition to conventional treatment, controlling the reproduction and absorption of bone is important (Deutschmann et al., 2005).

Epigallocatechin gallate (EGCg) is a constituent of green tea that has various bioactivities such as antibacterial activity (Toda et al., 1990), antioxidative activity (Lin & Lin, 1997), anticancer activity (carcinoma inhibition) (Brown, 1999), inhibition activity of blood glucose and blood pressure (Strobel et al., 2005; Ahn et al., 1999), and antiallergic activity (Maeda-Yamamoto et al., 2004). In particular, EGCg has anti-inflammatory effects, such as suppression of the activities of TNF and IL-1ß (Wheeler et al., 2004; Yang et al., 2001). We examined the effect of EGCg on osteoblasts to help determine the usefulness of EGCg for controlling inflammatory bone resorption.

Staphylococcus aureus is a major causative agent of human osteomyelitis (Lew & Waldvogel, 1999). It is a capable bone pathogen with adhesion molecules that facilitate its binding to the bone matrix (Boden & Flock, 1994; McDevitt et al., 1994) and toxin secretion that could stimulate bone resorption (Nair et al., 1995). Proinflammatory cytokines such as IL-1, IL-6 or TNF{alpha} are produced in S. aureus-induced osteomyelitis (Yoshii et al., 2002). Cytokines such as IL-6 or IL-12 were induced when osteoblasts were stimulated with S. aureus (Bost et al., 1999). Thus, we infected osteoblasts with S. aureus in vitro, and examined the effect of EGCg on the proinflammatory cytokines induced there. We also studied the suppression of RANKL expression.


   METHODS
TOP
 INTRODUCTION
 METHODS
RESULTS AND DISCUSSION
 REFERENCES
 
Cells and strain under test. We used NRG cells (provided by RIKEN cell bank) as the osteoblasts. NRG cells are a mouse marrow-derived fibroblast-like cell strain and have osteoblast-like features (Umezawa et al., 1992). They were cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco) with 10 % fetal bovine serum and 5 µg gentamicin ml–1 in 5 % CO2 at 37 °C

We used S. aureus 209P as the test strain for the experiment. The bacteria were cultured in tryptic soy broth (EIKEN).

Intracellular growth assay. NRG cells were distributed onto 48-well flat-bottom plates at 1x105cells per well. The cells were stimulated with EGCg (50, 100 and 200 µg ml–1) for 2 h before use in the intracellular growth assay. EGCg was provided by Dr Yukihiko Hara (Mitsui Norin Co., Ltd, Tokyo, Japan). After culturing for 2 h, the medium was replaced with EGCg-free, antibiotic-free culture medium with 10 % serum concentration.

Then we inoculated the cells with S. aureus at a m.o.i.=100 and centrifuged them at 450 g for 5 min to enhance the attachment of the bacteria to the NRG cells, and we incubated them at 37 °C for 2 h to facilitate the ingestion of the bacteria. Extracellular bacteria were removed by washing three times with PBS, and gentamicin was then added to the culture medium to achieve a concentration of 5 µg ml–1 (we reset the time at this point). After 0, 24 and 48 h culturing, we measured c.f.u. of viable intracellular bacteria using tryptic soy agar plates (Eiken).

Inflammatory cytokine assay. We detected proinflammatory cytokines using a partly modified method based on that reported by Wright & Friedland (2004). Namely, NRG cells were stimulated with EGCg (125 µg ml–1) for 2 h before the experiment. After replacing the media with antibiotic-free media, we inoculated the cells with S. aureus at a m.o.i.=100. Two hours later, we replaced the media with DMEM of 10 % serum concentration with 5 µg gentamicin ml–1 added. After 24 h culture, we measured the concentration of IL-1{alpha}, IL-1ß, IL-6 and TNF{alpha} in the culture supernatant. The measurement was conducted with Duo Set (R&D Systems) for IL-1{alpha} and OptEIA (BD Biosciences) for the others, based on its instruction manual.

Detection of RANKL. Pretreatment of osteoblasts with EGCg was conducted just as for the method of measuring proinflammatory cytokines. After the pretreatment, we detected the expression of RANKL over time with Western blotting. After 0, 2, 4, and 6 h culture, we removed the culture supernatant and homogenized the cells with lysis buffer (0.125 M Tris/HCl, 10 % 2-mercaptoethanol, 4 % SDS, 10 % sucrose and 0.004 % bromophenol blue). Each sample was analysed by SDS-PAGE using 10 % acrylamide gels and transferred to polyvinylidine difluoride membranes (Amersham Biosciences). After being blocked, the membranes were incubated with goat anti-rabbit RANKL antibody (R&D Systems). After being washed, the membranes were incubated with horseradish-peroxidase-conjugated rabbit anti-goat IgG (Zymed). The immunoreactive band was visualized with a chemiluminescence kit (GE Healthcare).

Statistical analysis. All assays for intracellular growth of S. aureus, measurement of inflammatory cytokines and detection of RANKL were independently repeated three times or more, and similar results were obtained. Representative data were expressed as means±SD of triplicate determinations. Student's t-test was used to determine the statistical significance. A P value <0.05 was considered statistically significant.


   RESULTS AND DISCUSSION
TOP
 INTRODUCTION
 METHODS
 RESULTS AND DISCUSSION
REFERENCES
 
Intracellular growth of S. aureus

The MIC of EGCg against S. aureus 209P was 250 µg ml–1 as we reported previously (Takahashi et al., 1995). In osteoblasts processed with 50, 100 or 200 µg ml–1, the intracellular growth of S. aureus progressed almost in the same way as in the unprocessed type (Fig. 1Go). Namely, the processing of NRG cells at an EGCg concentration less than the MIC had no effect on the intracellular growth of S. aureus, and hence we used 125 µg ml–1 to process the osteoblasts in the following experiments.


Figure 1
View larger version (15K):
[in this window]
[in a new window]

  		Fig. 1. Effect of EGCg on intracellular growth of S. aureus in NRG cells. The concentrations of EGCg used were 0 ({circ}), 50 (bullet), 100 ({square}) and 200 ({blacksquare}) µg ml–1. The number of bacteria was counted 0, 24 and 48 h after the start of the culture. The values are the means±SD for triplicate assays.

 
Effect of EGCg on the production of proinflammatory cytokines with osteoblasts infected by S. aureus

No proinflammatory cytokines were produced in NRG cells stimulated only with EGCg (Fig. 2Go). When NRG cells were inoculated with S. aureus, IL-1{alpha} and IL-6 were produced but not IL-1ß or TNF{alpha} (Fig. 2Go). IL-1ß and TNF{alpha} were also not produced when the cells were stimulated with LPS (data not shown). When NRG cells were processed with EGCg before being inoculated with S. aureus, the amount of IL-6 production after 24 h was 0 pg ml–1, which indicated a clear inhibition of production, in comparison to the IL-6 production (11.9 pg ml–1). In contrast, the production of IL-1{alpha} was slightly suppressed but no significant differences were shown. These results indicate that EGCg affects the osteoblast function in respect to production of IL-6.


Figure 2
View larger version (13K):
[in this window]
[in a new window]

  		Fig. 2. Production of inflammatory cytokines (a) IL-1{alpha}, (b) IL-1ß, (c) IL-6 and (d) TNF{alpha} in EGCg-processed and unprocessed NRG cells stimulated with S. aureus 209P (m.o.i.=100). The values are the means±SD for triplicate assays. An asterisk indicates that the P value was <0.05 for a comparison with the cytokine level in normal osteoblasts stimulated with S. aureus.

 
Detection of RANKL

Fig. 3Go shows the expression of RANKL when NRG cells were infected with S. aureus. We did not observe expression of RANKL before the cells were inoculated with S. aureus, but found a strong expression of RANKL after the inoculation irrespective of whether EGCg processing was performed or not. The expression of RANKL was observed in EGCg-processed NRG cells in 2, 4 or 6 h after they were inoculated with S. aureus, but was clearly less significant than that observed in NRG cells with no EGCg processing performed. It was thus demonstrated that EGCg-processed NRG cells inhibited the expression of RANKL.


Figure 3
View larger version (65K):
[in this window]
[in a new window]

  		Fig. 3. Expression of RANKL in EGCg-processed and unprocessed NRG cells stimulated with S. aureus 209P. RANKL was detected by Western blotting using anti-RANKL antibody. Lane A, normal NRG cells stimulated with S. aureus (m.o.i.=100); lane B, EGCg-treated (125 µg ml–1) NRG cells stimulated with S. aureus (m.o.i.=100); lane C, EGCg-treated (125 µg ml–1) NRG cells, not stimulated. Clear suppression of the RANKL expression was not found in the 2 h culture, but was found in the 4 h culture.

 
Few studies have been reported on the pathological condition of bacterial infection causing osteomyelitis; however, it has recently been clarified that S. aureus invades not only the surface of bones, but also into cells to induce its pathogenicity. S. aureus not only colonizes bone matrix, but also is internalized by osteoblasts. This has been demonstrated in vitro (Ellington et al., 1999) and in vivo (Reilly et al., 2000). Extensive work has delineated the mechanisms of S. aureus invasion, and the immune response resulting from its infection of osteoblasts (Ellington et al., 2003). The ability of S. aureus to invade and survive within osteoblasts may be critical to the observation that 80 % of all cases of chronic osteomyelitis are caused by S. aureus. Intracellular invasion provides protection from the humoral immune response and several classes of antibiotics. This could explain the persistence of the disease despite what has been considered adequate surgical and antibiotic management. Also in the present experiment, we noted the intracellular growth when NRG cells were inoculated with S. aureus (Fig. 1Go) and the promotion of the production of IL-6, IL-1{alpha} and RANKL, the important cytokines that contribute to bone resorption (Fig. 2Go). In bone marrow inflammation caused by infection with S. aureus, the production of various cytokines is locally induced. There are some reports on osteoblast cells, such as that IL-6 and IL-12 were produced in mouse osteoblast or MC3T3E-1 cells inoculated with S. aureus (Bost et al., 1999), and that IL-1ß or TNF{alpha} was not produced but IL-6 and RANKL were produced in mouse osteoblast cells inoculated with the Gram-positive coccus Streptococcus pyogenes (Okahashi et al., 2003). Our experimental results are consistent with these findings, and it is now clear that in osteoblast cells the production of cytokines, such as IL-1{alpha} and IL-6, is promoted not only by the stimulation on the cellular surface, but also by the stimulation inside the cells.

Catechin is an astringent constituent of green tea and its functions have been actively studied since the late 1980s. The catechin from green tea and the flavonoids of tea have bacteriostatic activity, antiviral activity, an antioxidant effect, antitumour activity, antiallergic activity, an immuno-enhancing effect, etc. In particular EGCg, which comprises 50–60 % of green tea catechin, is found to have anti-inflammatory effects inhibiting the expression of TNF and IL-1ß. In the present study, we examined the effect of EGCg on the induction of proinflammatory cytokine production in osteoblast cells infected with S. aureus, and found that it had no significant effect on the production of IL-1{alpha} but had certain effects on the inhibition of the production of IL-6 (Fig. 2Go) and of RANKL (Fig. 3Go).

Four signal cascades play roles in the induction of RANKL in osteoblasts: a signal cascade of activated vitamin D via VDR (Takasu et al., 2006), that of IL-6 and IL-11 via STAT 3 (O'Brien et al., 1999), that of PTH and PGE via cAMP/PKA for promoting the expression of RANKL genes (Kondo et al., 2002), and that of LPS and IL-1 via PKC-MEK/ERK (Kikuchi et al., 2001). In bacterial infection, pathogen-associated molecular patterns (PAMP) that are composed of bacteria are detected via Toll-like receptors (TLRs) and then the expression of RANKL genes is promoted through MEK/ERK, in the same way as that of IL-1 (Kikuchi et al., 2001). There should also be a system in our experiment that induces RANKL production via PKC-MEK/ERK, but we consider that the induction of RANKL production by this signal cascade was not significant because the production of IL-1 was small and because S. aureus-derived PAMP were not detected by TLR since the bacterial body resided inside the cells. Actually, it is reported that in macrophages and other cells, TLR develops on the surface of the cell and detects PAMP, and that fungus bodies such as LPS inside the cell cytoplasm are usually detected by Nod (Philpott & Girardin, 2004).

The inhibitory effect clarified in this study is a new finding on the bioactivity of EGCg. In our earlier reports we pointed out various antibacterial effects of EGCg, such as the antibacterial action of the simultaneous use of antibiotics and EGCg against meticillin-resistant S. aureus (Hu et al., 2002), and the antitoxic property of EGCg against staphylococcal enterotoxin B (Hisano et al., 2003). Others also reported the EGCg antibacterial effect on meticillin-resistant S. aureus (Kono et al., 1994) and on Pseudomonas aeruginosa and Escherichia coli, the causative bacteria of bone marrow inflammation (Yoda et al., 2004). Since EGCg can be used for bone cement for the treatment of bone marrow inflammation because of its property of stability against heat, our study indicates its additional effectiveness for the treatment in that EGCg suppresses bone resorption and has antibacterial effects.


   REFERENCES
TOP
 INTRODUCTION
 METHODS
 RESULTS AND DISCUSSION
 REFERENCES
 
Ahn, H. Y., Hadizadeh, K. R., Seul, C., Yun, Y. P., Vetter, H. & Sachinidis, A. (1999). Epigallocathechin-3 gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172). Mol Biol Cell 10, 1093–1104.[Abstract/Free Full Text]

Azuma, Y., Kaji, K., Katogi, R., Takeshita, S. & Kudo, A. (2000). Tumor necrosis factor-{alpha} induces differentiation of and bone resorption by osteoclasts. J Biol Chem 275, 4858–4864.[Abstract/Free Full Text]

Boden, M. K. & Flock, J. I. (1994). Cloning and characterization of a gene for a 19 kDa fibrinogen-binding protein from Staphylococcus aureus. Mol Microbiol 12, 599–606.[CrossRef][Medline]

Bost, K. L., Ramp, W. K., Nicholson, N. C., Bento, J. L., Marriott, I. & Hudson, M. C. (1999). Staphylococcus aureus infection of mouse or human osteoblasts induces high levels of IL-6 and IL-12 production. J Infect Dis 180, 1912–1920.[CrossRef][Medline]

Brown, M. D. (1999). Green tea (Camellia sinensis) extract and its possible role in the prevention of cancer. Altern Med Rev 4, 360–370.[Medline]

Deutschmann, A., Mache, C. J., Bodo, K., Zebedin, D. & Ring, E. (2005). Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor-{alpha} blockage. Pediatrics 116, 1231–1233.[Abstract/Free Full Text]

Ellington, J. K., Reilly, S. S., Ramp, W. K., Smeltzer, M. S., Kellam, J. F. & Hudson, M. C. (1999). Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Microb Pathog 26, 317–323.[CrossRef][Medline]

Ellington, J. K., Harris, M., Webb, L., Smith, B., Smith, T., Tan, K. & Hudson, M. C. (2003). Intracellular Staphylococcus aureus: a mechanism for the indolence of osteomyelitis. J Bone Joint Surg Br 85, 918–921.[Medline]

Hisano, M., Yamaguchi, K., Inoue, Y., Iijima, M., Adachi, M. & Shimamura, T. (2003). Inhibitory effect of catechin against the superantigen staphylococcal enterotoxin B (SEB). Arch Dermatol Res 295, 183–189.[CrossRef][Medline]

Hu, Z. Q., Zhao, W. H., Asano, N., Yoda, Y., Hara, Y. & Shimamura, T. (2002). Epigallocatechin gallate synergistically enhances the activity of carbapenems against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 46, 558–560.[Abstract/Free Full Text]

Jimi, E., Nakamura, I., Duong, L. T., Ikebe, T., Takahashi, N., Rodan, G. A. & Suda, T. (1999). Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of osteoblasts/stromal cells. Exp Cell Res 247, 84–93.[CrossRef][Medline]

Kikuchi, T., Matsuguchi, T., Tsuboi, N., Mitani, A., Tanaka, S., Matsuoka, M., Yamamoto, G., Hishikawa, T., Noguchi, T. & Yoshikai, Y. (2001). Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. J Immunol 166, 3574–3579.[Abstract/Free Full Text]

Kobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., Nakagawa, N., Kinosaki, M., Yamaguchi, K. & other authors (2000). Tumor necrosis factor {alpha} stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 191, 275–286.[Abstract/Free Full Text]

Kondo, H., Guo, J. & Bringhurst, F. R. (2002). Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells. J Bone Miner Res 17, 1667–1679.[CrossRef][Medline]

Kono, K., Tatara, I., Takeda, S., Arakawa, K. & Hara, Y. (1994). Antibacterial activity of epigallocatechin gallate against methicillin-resistant Staphylococcus aureus. Kansenshogaku Zasshi 68, 1518–1522.[Medline]

Lew, D. P. & Waldvogel, F. A. (1999). Use of quinolones in osteomyelitis and infected orthopaedic prosthesis. Drugs 58 (Suppl. 2), 85–91.

Lin, Y.-L. & Lin, J.-K. (1997). (–)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-{kappa}B. Mol Pharmacol 52, 465–472.[Abstract/Free Full Text]

Maeda-Yamamoto, M., Inagaki, N., Kitaura, J.,, Chikumoto, T., Kawahara, H., Kawakami, Y., Sano, M., Miyase, T., Tachibana, H. & other authors (2004). O-methylated catechins from tea leaves inhibit multiple protein kinases in mast cells. J Immunol 172, 4486–4492.[Abstract/Free Full Text]

McDevitt, D., Francois, P., Vaudaux, P. & Foster, T. J. (1994). Molecular characterization of the clumping factor (fibrinogen receptor) of Staphylococcus aureus. Mol Microbiol 11, 237–248.[Medline]

Morris, S. K., Brophy, J., Richardson, S. E., Summerbell, R., Parkin, P C., Jamieson, F., Limerick, B., Wiebe, L. & Ford-Jones, E. L. (2006). Blastomycosis in Ontario, 1994–2003. Emerg Infect Dis 12, 274–279.[Medline]

Nair, S., Song, Y., Meghji, S., Reddi, K., Harris, M., Ross, A., Poole, S., Wilson, M. & Henderson, B. (1995). Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity. J Bone Miner Res 10, 726–734.[Medline]

O'Brien, C. A., Gubrij, I., Lin, S.-C., Saylors, R. L. & Manolagas, S. C. (1999). STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-{kappa}B ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone. J Biol Chem 274, 19301–19308.[Abstract/Free Full Text]

Okahashi, N., Sakurai, A., Nakagawa, I., Fujiwara, T., Kawabata, S., Amano, A. & Hamada, S. (2003). Infection by Streptococcus pyogenes induces the receptor activator of NF-{kappa}B ligand expression in mouse osteoblastic cells. Infect Immun 71, 948–955.[Abstract/Free Full Text]

Philpott, D. J. & Girardin, S. E. (2004). The role of Toll-like receptors and Nod proteins in bacterial infection. Mol Immunol 41, 1099–1108.[CrossRef][Medline]

Reilly, S. S., Hudson, M. C., Kellam, J. F. & Ramp, W. K. (2000). In vivo internalization of Staphylococcus aureus by embryonic chick osteoblasts. Bone 26, 63–70.[Medline]

Sax, H. & Lew, D. (1999). Osteomyelitis. Curr Infect Dis Rep 1, 261–266.[Medline]

Strobel, P., Allard, C., Perez-Acle, T., Calderon, R., Aldunate, R. & Leighton, F. (2005). Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochem J 386, 471–478.[CrossRef][Medline]

Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T. & Martin, T. J. (1999). Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20, 345–357.[Abstract/Free Full Text]

Takahashi, O., Cai, Z., Toda, M., Hara, Y. & Shimamura, T. (1995). Appearance of antibacterial activity of oxacillin against methicillin resistant Staphylococcus aureus (MRSA) in the presence of catechin. Kansenshogaku Zasshi 69, 1126–1134.[Medline]

Takasu, H., Sugita, A., Uchiyama, Y., Katagiri, N., Okazaki, M., Ogata, E. & Ikeda, K. (2006). c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs. J Clin Invest 116, 528–535.[CrossRef][Medline]

Toda, M., Okubo, S., Ikigai, H. & Shimamura, T. (1990). Antibacterial and anti-hemolysin activities of tea catechins and their structural relatives. Nippon Saikingaku Zasshi 45, 561–566.[Medline]

Umezawa, A., Maruyama, T., Segawa, K., Shadduck, R. K., Waheed, A. & Hata, J. (1992). Multipotent marrow stromal cell line is able to induce hematopoiesis in vivo. J Cell Physiol 151, 197–205.[CrossRef][Medline]

Wheeler, D. S., Catravas, J. D., Odoms, K., Denenberg, A., Malhotra, V. & Wong, H. R. (2004). Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1ß-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr 134, 1039–1044.[Abstract/Free Full Text]

Wright, K. M. & Friedland, J. S. (2004). Regulation of chemokine gene expression and secretion in Staphylococcus aureus-infected osteoblasts. Microbes Infect 6, 844–852.[CrossRef][Medline]

Yang, F., Oz, H. S., Barve, S., de Villiers, W. J., McClain, C. J. & Varilek, G. W. (2001). The green tea polyphenol (–)-epigallocatechin-3-gallate blocks nuclear factor-{kappa}B activation by inhibiting I{kappa}B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol 60, 528–533.[Abstract/Free Full Text]

Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S., Tomoyasu, A., Yano, K., Goto, M. & other authors (1998). Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95, 3597–3602.[Abstract/Free Full Text]

Yoda, Y., Hu, Z. Q., Zhao, W. H. & Shimamura, T. (2004). Different susceptibilities of Staphylococcus and Gram-negative rods to epigallocatechin gallate. J Infect Chemother 10, 55–58.[CrossRef][Medline]

Yoshii, T., Magara, S., Miyai, D., Nishimura, H. & Kuroki, E. (2002). Local levels of interleukin-1ß, -4, -6 and tumor necrosis factor {alpha} in an experimental model of murine osteomyelitis due to Staphylococcus aureus. Cytokine 19, 59–65.[CrossRef][Medline]




This article has been cited by other articles:


Home page
 Infect. Immun.Home page
S. N. Somayaji, S. Ritchie, M. Sahraei, I. Marriott, and M. C. Hudson
Staphylococcus aureus Induces Expression of Receptor Activator of NF-{kappa}B Ligand and Prostaglandin E2 in Infected Murine Osteoblasts
Infect. Immun., November 1, 2008; 76(11): 5120 - 5126.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishida, I.
Right arrow Articles by Shimamura, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishida, I.
Right arrow Articles by Shimamura, T.
Agricola
Right arrow Articles by Ishida, I.
Right arrow Articles by Shimamura, T.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL J MED MICROBIOL MICROBIOLOGY J GEN VIROL ALL SGM JOURNALS