| 1. |
Yamato H, Sanui T, Yotsumoto K, Nakao Y, Watanabe Y, Hayashi C, Aihara R, Iwashita M, Tanaka U, Taketomi T, Fukuda T, Nishimura F., Combined application of geranylgeranylacetone and amelogenin promotes angiogenesis and wound healing in human periodontal ligament cells., Journal of Cellular Biochemistry, doi: 10.1002/jcb.29903., 2021.02. |
| 2. |
Yotsumoto K, Sanui T, Tanaka U, Yamato H, Alshargabi R, Shinjo T, Nakao Y, Watanabe Y, Hayashi C, Taketomi T, Fukuda T, Nishimura F, Amelogenin downregulates interferon gamma-induced major histocompatibility complex class II expression through suppression of euchromatin formation in the class II transactivator promoter IV region in macrophages., Frontiers in Immunology, doi.org/10.3389/fimmu.2020.00709, 11, 709-709, 2020.03. |
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Sanui T, Fukuda T, Tanaka U, Toyoda K, Yotsumoto K, Nakao Y, Yamato H, Taketomi T, Nishimura F, Sprouty2 Inhibition Resolves Inflammation in Periodontal Disease and Creates a Suitable Environment for Periodontal Tissue Regeneration., Journal of Cell Biology & Immunology, 1, 101-101, 2017.11. |
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Terukazu Sanui, Masaaki Takeshita, Takao Fukuda, Urara Tanaka, Rehab Alshargabi, Yoshitomi Aida, Fusanori Nishimura, Roles of serum in innate immune responses of human leukocytes to synthetic lipopeptide, International Immunopharmacology, 10.1016/j.intimp.2017.06.006, 50, 61-68, 2017.09, Tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 (Pam3CSK4) is a highly conserved molecular motif found in various classes of lipoproteins. The requirement for leukocyte to respond to synthetic Pam3CSK4 were studied. Pam3CSK4 primed neutrophils for a respiratory burst in a serum-dependent manner. Pam3CSK4 upregulated CD11b, CD14, and cytochrome b558, and downregulated Leu-8. Treatment of neutrophils with anti-CD14 antibodies and treatment of serum with anti-LPS binding protein (LBP) antibodies resulted in the inhibition of priming for respiratory burst by Pam3CSK4. It should be noted that LBP could not replicate the effects of serum in priming of neutrophils for respiratory burst by Pam3CSK4. Serum LBP bound to immobilized Pam3CSK4. Pam3CSK4 induced the interleukin-8 (IL-8) production by leukocytes in a serum-dependent manner. Further, Pam3CSK4-induced priming of neutrophils for respiratory burst was not inhibited by the LPS antagonists LA-14-PP, Rhodobacter sphaeroides LPS, or E5531, and Pam3CSK4-induced IL-8 production by leukocytes was not affected by LPS antagonist, E5531, indicating that Pam3CSK4 was recognized by a different receptor than LPS. Thus, Pam3CSK4 and LPS had similar biological activities and similar requirement to act on leukocytes, but were recognized by different receptors. Serum in the action of Pam3CSK4 on leukocytes was not replicated by LBP, suggesting that Pam3CSK4 might be disaggregated by serum to result in the activation of leukocytes.. |
| 5. |
Terukazu Sanui, Masaaki Takeshita, Takao Fukuda, Urara Tanaka, Rehab Alshargabi, Yoshitomi Aida, Fusanori Nishimura, Adhesion attenuates respiratory burst induced by different modes of triggering in resting or LPS-primed neutrophils, Immunobiology, 10.1016/j.imbio.2017.05.001, 222, 8-9, 865-871, 2017.08, The effects of adherence on neutrophil superoxide anion (O2 −) generation triggered by surface, soluble ligand, or adherence were studied. Resting-neutrophils adhered to the uncoated tubes resulting in O2 − generation, but not on plasma-, fibrinogen-, vitronectin-, fibronectin-, laminin-, collagen-, or poly HEMA-coated surfaces. Enhanced N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated O2 − generation by LPS-primed-neutrophils was induced by the incubation on plasma, fibrinogen, vitronectin, fibronectin, or laminin in the absence of Mg2+. In the presence of Mg2+, this response was observed in cells on collagen or poly HEMA. LPS-primed-neutrophils adhered to uncoated, BSA- or IgG-coated tubes and did not respond to fMLP, indicating that the fMLP-response of LPS-primed-neutrophils was suppressed by adherence. Upon incubation on plasma, fibrinogen, vitronectin, fibronectin in the presence of Mg2+, LPS-primed-neutrophils showed O2 − generation. Upon incubation on collagen or poly HEMA, the primed-neutrophils neither generated O2 − nor adhered. We found that O2 − response of LPS-primed-neutrophils was attenuated depending on the time of exposure to plasma-coated surface. This attenuation was evident on plasma or fibrinogen, but not on collagen in the presence of Mg2+, indicating that O2 − generation by LPS-primed-neutrophils was attenuated dependent on adherence but not on Mg2+. Thus, adhesion attenuated the O2 − generation triggered by both soluble (fMLP) and insoluble (surface) stimuli.. |
| 6. |
Terukazu Sanui, 福田 隆男, 山道 研介, Kyosuke Toyoda, Urara Tanaka, 四本 かれん, 武富 孝治, 西村 英紀, Microarray analysis of the effects of amelogenin on U937 monocytic cells., American Journal of Molecular Biology, in press, 2017.04. |
| 7. |
Terukazu Sanui, Masaaki Takeshita, Takao Fukuda, Akira Haraguchi, Yoshitomi Aida, Fusanori Nishimura, Anti-CD14 Antibody-treated Neutrophils Respond to LPS
Possible Involvement of CD14 Upregulated by Anti-CD14 Antibody Binding, Immunological Investigations, 10.1080/08820139.2016.1238925, 46, 2, 190-200, 2017.02, CD14 and Toll-like receptor 4/MD2 (TLR4/MD2) mediate the action of LPS on neutrophils. The anti-CD14 antibody and the TLR4/MD2-antagonist, synthetic lipid IVa (LA-14-PP), are known to inhibit the response of neutrophils to LPS. We studied the role of CD14 in LPS-induced priming of neutrophils for enhanced release of the superoxide anion. The anti-CD14 antibody at much higher concentrations than required to saturate CD14 was required to inhibit priming by LPS. The inhibitory effect of the anti-CD14 antibody was overcome by LPS. After washing, anti-CD14-treated neutrophils showed upregulated CD14 upon incubation at 37°C and responded to LPS with a delayed time-course. Thus, CD14-blocked neutrophils gained responsiveness to LPS through newly upregulated CD14. These results suggested that the unbound/free anti-CD14 antibody was essential to inhibit LPS-induced priming by blocking CD14 that were newly expressed during incubation at 37°C. LA-14-PP inhibited the response of neutrophils to LPS in an anti-CD14 antibody sensitive manner. When neutrophils were treated with LA-14-PP followed by treatment with the anti-CD14 antibody, CD14 was upregulated upon warming, but priming was blocked, suggesting that TLR4/MD2 was not newly expressed by warming in association with CD14 molecules. Thus, in addition to blocking CD14, the anti-CD14 antibody was found to induce the expression of new CD14.. |
| 8. |
Terukazu Sanui, 福田 隆男, Urara Tanaka, Kyosuke Toyoda, 山道 研介, 張 祥翼, 武富 孝治, 西村 英紀, Biological effects of Sprouty2 inhibition in periodontal ligament cells., Journal of Cell Signaling, 10.4172/jcs.1000117, 1, 117, 2016.07. |
| 9. |
Terukazu Sanui, Urara Tanaka, Takao Fukuda, Kyousuke Toyoda, Takaharu Taketomi, Ryo Atomura, Kensuke Yamamichi, Fusanori Nishimura, Mutation of Spry2 Induces Proliferation and Differentiation of Osteoblasts but Inhibits Proliferation of Gingival Epithelial Cells, Journal of Cellular Biochemistry, 10.1002/jcb.25014, 116, 4, 628-639, 2015.04, Sprouty was identified as an inhibitor of the fibroblast growth factor (FGF) receptor, and Sprouty2 (Spry2) functions as a negative regulator of receptor tyrosine kinase signaling. In this study, we investigated how inhibition of Spry2 affects osteoblasts and gingival epithelial cells in periodontal tissue regeneration in vitro. Transduction of a dominant-negative mutant of Spry2 (Y55A-Spry2) enhanced basic fibroblast growth factor (bFGF)- and epidermal growth factor (EGF)-induced ERK activation in MC3T3-E1 osteoblastic cells. In contrast, it decreased their activation in GE1 cells. Consistent with these observations, Y55A-Spry2 increased osteoblast proliferation with bFGF and EGF stimulation, whereas the proliferation of Y55A-Spry2-introduced GE1 cells was decreased via the ubiquitination and degradation of EGF receptors (EGFRs). In addition, Y55A-Spry2 caused upregulation of Runx2 expression and downregulation of Twist, a negative regulator of Runx2, with treatment of bFGF and EGF, resulting in enhanced osteoblastogenesis accompanied by alkaline phosphatase activation and osteocalcin expression in MC3T3-E1 cells. These data suggest that suppression of Spry2 expression induces proliferation and differentiation of osteoblastic cells after the addition of a bFGF and EGF cocktail but inhibits proliferation in gingival epithelial cells. These in vitro experiments may provide a molecular basis for novel therapeutic approaches in periodontal tissue regeneration. Taken together, our study proposes that combined application of an inhibitor for tyrosine 55 of Spry2, bFGF, and EGF may effectively allow alveolar bone growth and block the ingrowth of gingival epithelial cells toward bony defects, biologically mimicking a barrier effect in guided tissue regeneration, with in vivo investigation in the future. J. Cell. Biochem. 116: 628-639, 2015.. |
| 10. |
讃井 彰一, 福田 隆男, 田中 麗, 豊田 敬介, 武富 孝治, 西村 英紀, Spry2 is a novel therapeutic target for periodontal tissue regeneration through fibroblast growth factor receptor signaling and epidermal growth factor signaling, Receptors & Clinical Investigation, 10.14800/rci.597, e597-e597, 2015.03. |
| 11. |
Terukazu Sanui, R. L. Gregory, Analysis of Streptococcus mutans biofilm proteins recognized by salivary immunoglobulin A, Molecular Oral Microbiology, 10.1111/j.1399-302X.2009.00523.x, 24, 5, 361-368, 2009.10, Introduction: The purpose of this study was to examine the Streptococcus mutans biofilm cellular proteins recognized by immunoglobulin A (IgA) in saliva from various caries-defined populations. Methods: Biofilm and planktonic S. mutans UA159 cells were prepared. The proteins were extracted, separated by two-dimensional gel electrophoresis, transferred to blotting membranes, and probed for IgA using individual saliva samples from three groups of subjects; those who developed 0 caries (no active caries), 5-9 caries (medium), or more than 10 caries (severe) over a 12-month interval. Results: Several proteins were recognized by salivary IgA in all groups of saliva but spot distribution and intensity varied greatly between the groups, and some proteins were recognized more strongly in biofilm cells than in planktonic culture, and vice versa. Furthermore, 15 proteins were only recognized by saliva from the 'no active caries' group, and four proteins were recognized by saliva samples from subjects in all three groups. Specifically, antigen I/II was recognized less in biofilm cells by caries-free saliva compared with planktonic cells. However, salivary IgA antibody to antigen I/II was absent in blots using saliva from the 'medium caries' and 'severe caries' groups. Conclusion: The bacterial molecules recognized by caries-free saliva are significant factors for S. mutans caries formation, and their inhibition could be a therapeutic target. In addition, saliva of caries-free subjects includes significant IgA antibody against antigen I/II of S. mutans, indicating a protective mechanism. However, microorganisms may protect themselves from host immune attack by forming biofilms and decreasing expression of antigen I/II.. |
| 12. |
Terukazu Sanui, Ayumi Inayoshi, Mayuko Noda, Eiko Iwata, Jens V. Stein, Takehiko Sasazuki, Yoshinori Fukui, DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1, Blood, 10.1182/blood-2003-01-0173, 102, 8, 2948-2950, 2003.10, Although the migratory property of lymphocytes is critical for protective immunity, tissue infiltration of lymphocytes sometimes causes harmful immune responses. DOCK2 plays a critical role in lymphocyte migration by regulating actin cytoskeleton through Rac activation, yet the mechanism by which DOCK2 activates Rac remains unknown. We found that DOCK2 associates with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain. When DOCK2 was expressed in T-hybridoma cells lacking endogenous expression of DOCK2, Rac activation and actin polymerization were induced. However, such responses were not elicited by the DOCK2 mutant lacking the region required for ELMO1 binding. On the other hand, we found that the expression of ELMO1 induces Rac activation in the plasmacytoma cells expressing DOCK2 but not ELMO1. These results indicate that the association of DOCK2 with ELMO1 is critical for DOCK2-mediated Rac activation, thereby suggesting that their association might be a therapeutic target for immunologic disorders caused by lymphocyte infiltration.. |
| 13. |
Terukazu Sanui, Ayumi Inayoshi, Mayuko Noda, Eiko Iwata, Masahiro Oike, Takehiko Sasazuki, Yoshinori Fukui, DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, in T cells, Immunity, 10.1016/S1074-7613(03)00169-9, 19, 1, 119-129, 2003.07, DOCK2 is a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City which are known to regulate actin cytoskeleton. DOCK2 is critical for lymphocyte migration, yet the role of DOCK2 in TCR signaling remains unclear. We show here that DOCK2 is essential for TCR-mediated Rac activation and immunological synapse formation. In DOCK2-deficient T cells, antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, to the APC interface was severely impaired, resulting in a significant reduction of antigen-specific T cell proliferation. In addition, we found that the efficacy of both positive and negative selection was reduced in DOCK2-deficient mice. These results suggest that DOCK2 regulates T cell responsiveness through remodeling of actin cytoskeleton via Rac activation.. |
