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Journal of Orthopaedic Science 07/2011; · 0.84 Impact Factor
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Nahoko Kato-Kogoe,
Hideki Ohyama,
Fusanori Nishimura,
Michio Meguro, Sayuri Yoshizawa,
Yuka Okada,
Keiji Nakasho,
Koji Yamanegi,
Naoko Yamada,
Masaki Hata,
Takehiro Higashi,
Nobuyuki Terada,
Sho Matsushita
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ABSTRACT: Fibroblasts act as important immune regulatory cells via their ability to cross-talk with T cells accumulating in lesions. Our previous study showed that fibroblasts produce several cytokines and chemokines by crosslinking HLA class II (HLA-II) molecules with monoclonal antibodies or by making T-cell receptor-peptide-HLA complexes. It is thus conceivable that the interaction of T cells and fibroblasts via HLA-II affects fibroblast responses to stimuli. This study used human gingival fibroblasts (HGF) to investigate possible effects of these fibroblast-derived soluble factors on the differentiation of naïve T cells and on the subsequent fibroblast responses. After mixed lymphocyte reaction culture between naïve T cells and allogeneic dendritic cells in the presence of culture supernatant from HGF stimulated via HLA-DQ molecules (DQ-sup), but not via DR, T cells exhibited a Th2-shifted phenotype, thereby producing quantitatively more IL-13 and IL-5 compared with interferon-γ. Astonishingly, analyses to identify possible factors affecting the Th2 polarization secreted from HLA-II-stimulated HGF, prostaglandin E₂, was detected only in DQ-sup. The Th2 polarization of naïve T cells was blocked in the presence of supernatants from indomethacin-treated HGF with HLA-DQ stimulation. In addition, we found that the culture supernatants of Th cells activated following mixed lymphocyte reaction culture in the presence of DQ-sup had the potential to induce gene expression of type I and III collagens in HGF. These results suggested that fibroblasts stimulated via HLA-DQ molecules promote Th2 polarization in Th-cell responses and showed the counter activation of collagen synthesis, implicating orchestrated responses among these cells in the fibrosis of chronic inflammatory lesions.
Laboratory Investigation 12/2010; 90(12):1747-56. · 3.64 Impact Factor
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ABSTRACT: In recent years, calcium phosphate cements (CPCs) have frequently been used as bone substitutes in the field of orthopedic surgery. When CPC is used as a bone substitute in vivo, blood contamination is unavoidable. To date, however, no detailed study has been conducted focusing on how the physical properties of CPCs would change under the influence of blood. In this study, the effects of blood contamination on Biopex-R (BPR, PENTAX, Tokyo) are examined in vitro and in vivo. The compressive strength of BPR after setting decreased depending on the amount of contaminating blood. The BPR, which has set in vivo, not only has a fragile surface due to the contamination by blood, but also has a propensity to shorten and be destroyed during the early postoperative stage, especially in the bone exposed to loads. On the other hand, radiographic and histological features in vivo indicated that the absorption and the bone replacement of BPR were stimulated by blood contamination. In the clinical evaluation, the patient's own peripheral venous blood was added to the BPR. One year after the surgery, the absorption was noted around the hardened BPR. To advance CPCs (including BPR) as bioabsorbable bone replaceable materials, it is essential to utilize the patient's own blood in combination with the CPC.
Journal of Biomedical Materials Research Part B Applied Biomaterials 11/2009; 92(1):95-101. · 2.15 Impact Factor
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ABSTRACT: Recent studies suggested macrophages were integrated in adipose tissues, interacting with adipocytes, thereby exacerbating inflammatory responses. Persistent low-grade infection by gram-negative bacteria appears to promote atherogenesis. We hypothesized a ligand for toll-like receptor 4 (TLR4), bacterial lipopolysaccharide (LPS), would further exaggerate macrophage-adipocyte interaction.
RAW264.7 macrophage cell line and differentiated 3T3-L1 preadipocytes were co-cultured using transwell system. As a control, each cell was cultured independently. After incubation of the cells with or without Escherichia coli LPS, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production was evaluated.
Co-culture of macrophages and adipocytes with low concentration of Escherichia coli LPS (1 ng/mL) markedly up-regulated IL-6 production (nearly 100-fold higher than that of adipocyte culture alone, p < 0.01), whereas TNF-alpha production was not significantly influenced. This increase was partially inhibited by anti-TNF-alpha neutralizing antibody. Recombinant TNF-alpha and LPS synergistically up-regulated IL-6 production in adipocytes. However, this increase did not reach the level of production observed in co-cultures stimulated with LPS.
A ligand for TLR-4 stimulates macrophages to produce TNF-alpha. TNF-alpha, thus produced, cooperatively up-regulates IL-6 production with other soluble factors secreted either from adipocytes or macrophages in these cells. Markedly up-regulated IL-6 would greatly influence the pathophysiology of diabetes and its vascular complications.
Obesity 12/2007; 15(11):2549-52. · 4.28 Impact Factor
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ABSTRACT: Diabetic subjects are susceptible to atherosclerosis. It has been postulated that inflammation plays a crucial role in atherogenesis. Since previous studies suggested persistent low-grade infection by Gram-negative bacteria such as Chlamydia spp. and/or periodontal infection is associated with increased atherogenesis among diabetic subjects, we hypothesized that macrophages under hyperglycemia respond to lipopolysaccharide (LPS) challenge in a more exaggerated manner than under normal glucose conditions. Therefore, we examined cytokine productivity and associated signal transduction molecules in LPS-stimulated the monocytic cell line THP-1, under conditions of hyperglycemia. Differentiated THP-1 cells were cultured under normal and high glucose conditions without fetal bovine serum, and were stimulated with Escherichia coli LPS in the presence of LPS binding protein. Following stimulation, activated signal transduction molecules were detected by protein microarray and confirmed thereafter. Results indicated that c-jun N-terminal kinase (JNK) was highly-phosphorylated at high glucose concentrations, and this was confirmed by Western-immunoblotting. Tumor necrosis factor-alpha and monocyte chemo-attractant protein-1 production were significantly enhanced under these conditions. SP600125, a selective inhibitor of JNK, dose-dependently suppressed the production of these cytokine. Therefore, we suggest that this may be one of the mechanisms by which sub-clinical infection by Gram-negative bacteria promotes atherosclerosis in diabetic subjects.
Journal of Endotoxin Research 02/2007; 13(4):227-34. · 3.06 Impact Factor
