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生命の根源的な特性として恒常性（ホメオスタシス）があり、私達の健康維持にも必須のものです。しかし周囲の環境は常に変化するため、恒常性の維持は細胞内外の常に動的な変化によってのみ維持することが可能になります。古い細胞は新しい細胞に置き換えられ、細菌やウィルスなどの外敵の侵入にも備えなければなりません。
私達の口腔生化学講座は、生命の恒常性に関わる①細胞分化と②免疫応答に焦点をあて、その分子メカニズムを明らかにすることを目標にしています。新たな分子機構の解明は、病気の予防や治療のための分子標的の発見に繋がります。私達は、生命現象の分子機構に興味があり、一緒に研究できる大学院生（博士＆修士課程）を募集しています。

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主な研究実績

松口徹也

1. Kusuyama J, Bandow K, Shamoto M, Kakimoto K, Ohnishi T, and Matsuguchi T. Low Intensity Pulsed Ultrasound (LIPUS) Influences the Multilineage Differentiation of Mesenchymal Stem and Progenitor Cell Lines through ROCK-Cot/Tpl2-MEK-ERK Signaling Pathway. J. Biol. Chem. 289:10330-44, 2014.
2. Matsuguchi T. Mast Cells as Critical Effectors of Host Immune Defense against Gram-negative Bacteria. Curr Med Chem. 19: 1432-1442, 2012.
3. Musikacharoen T, Bandow K, Kakimoto K, Kusuyama J, Onishi T, Yoshikai Y, Matsuguchi T. Functional involvement of dual specificity phosphatase 16 (DUSP16), a c-Jun N-terminal kinase-specific phosphatase, in the regulation of T helper cell differentiation. J Biol Chem. 2011 Jul 15;286(28):24896-905, 2011.
4. Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T. JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation. J Bone Miner. Res. 24, 398-410, 2009.
5. Musikacharoen T, Oguma A, Yoshikai Y, Chiba N, Masuda A, Matsuguchi T.: Interleukin-15 induces IL-12 receptor beta1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. Blood 105, 711-720, 2005
6. Sugimoto K, Ohata M, Miyoshi J, Ishizaki H, Tsuboi N, Masuda A, Yoshikai Y, Takamoto M, Sugane K, Matsuo S, Shimada Y, Matsuguchi T.: A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation. J. Clin. Invest. 114, 857-866, 2004
7. Hermoso MA, Matsuguchi T, Smoak K, Cidlowski JA.: Glucocorticoids and tumor necrosis factor alpha cooperatively regulate toll-like receptor 2 gene expression. Mol. Cell. Biol. 24, 4743-4756, 2004
8. Matsuguchi, T., Masuda, A., Sugimoto, K., Nagai, Y., Yoshikai, Y. : JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation. EMBO J., 22, 4455-4464, 2003
9. Matsuguchi, T.., Musikacharoen, T., Johnson, T.. R., Kraft, A. S., Yoshikai, Y.: A Novel MAP Kinase Phosphatase is an Important Negative Regulator of LPS-mediated JNK activation in Mouse Macrophage Cell Lines. Mol. Cell. Biol., 21, 6999-7009, 2001
10. Matsuguchi, T.., Takagi, K., Musikacharoen, T., Yoshikai, Y.: Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes. Blood 95, 1378-1385, 2000.

大西智和

1. Ohnishi T, Bandow K, Kakimoto K, Kusuyama J, Matsuguchi T; Long-time treatment by low-dose N-acetyl-L-cysteine enhances proinflammatory cytokine expressions in LPS-stimulated macrophages. PLoS One2014; 9: e87229
2. Ohnishi T., Bandow K., Matsuguchi T. Involvement of Cot/Tpl2 in bone loss during periodontitis. J Dental Res 2010 89 192-197.
3. Ohnishi T, Bandow K, Matsuguchi T Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes. J Periodontal Res. 2009; 44(1):43-51.
4. Ohnishi T., Kakimoto K. Bandow, Lowenstein C. J., Daikuhara Y, Matsuguchi T. Mature hepatocyte growth factor / scatter factor on the surface of human granulocytes is released by a mechanism involving activated factor Xa. J Immunology. 176(11):6945-6953
5. Padalko E, Ohnishi T, Matsushita K, Sun H, Fox-Talbot K, Bao C, Baldwin WM 3rd, Lowenstein CJ. Peroxynitrite inhibition of Coxsackievirus infection by prevention of viral RNA entry. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11731-6.
6. Ohnishi T., Daikuhara Y, Hepatocyte growth factor/scatter factor in development, inflammation and carcinogenesis: its expression and role in oral tissues. Arch Oral Biol, 48, 797-804, 2003
7. Ohnishi T., Daikuhara Y, Hepatocyte growth factor in oral biology Dentistry in Japan, 39, 48-51, 2003,
8. Ohnishi T., Kakimoto K, Hashida S, Fujii M, Hirono S, Nishiyama K, Amita Y, Ishikawa E, Tsubouchi H, Daikuhara Y. Development of highly sensitive enzyme-linked immunosorbent assays for hepatocyte growth factor/scatter factor (HGF/SF): determination of HGF/SF in serum and urine from normal human subjects. J Immunol Methods, 244, 163-173, 2000
9. Ohnishi T., Suwa, M. Oyama T., Arakaki N., Torii M., Daikuhara Y., Prostaglandin E2 predominantly induces production of hepatocyte Growth factor/scatter factor in human dental pulp in acute inflammation. J Dent Res, 79, 784-755, 1999
10. Ohnishi T., Nakamura O., Arakaki N., Daikuhara Y. Effect of phosphorylated rat fetuin on the growth of hepatocytes in primary culture in the presence of human hepatocyte-growth factor. Evidence that phosphorylated fetuin is modulator of hepatocyte-growth factor. Eur J Biochem, 243, 753-761, 1997.

千葉紀香

1. Ray S, Chiba N, Yao C, Guan X, McConnell AM, Brockway B, Que L, McQualter JL, Stripp BR, Rare SOX2+ airway progenitor cells generate KRT5+ cells that repoplulate damaged alveolar parenchyma following influenza virus infection.  Stem Cell Reports, 7 (5): 817-825, 2016
2. Chiba N, Shimada K, Chen S, Jones HD, Alsabeh R, Slepenkin AV, Peterson E, Crother TR, Arditi M,  Mast cells play an important role in Chlamydia pneumoniae lung infection by facilitating immune cell recruitment into the airway.  J Immunol., 194 (8): 3840-3851, 2015
3. Lee YH, Schulte DJ, Shimada K, Chen S, Crother TR, Chiba N, Fishbein MC, Lehman TJA, Aridit M,  Interleukin-1b is crucial for the induction of coronary artery inflammation in a mouse model of Kawasaki disease.  Circulation, 125 (12): 1542-1550, 2012
4. Shimada K, Crother TR, Karlin J, Dagvadrj J, Chiba N, Chen S, Rmanujan VK, Wolf AJ, Vergnes L, Ojcius DM, Rentsendorj A, Vargas M, Guerrero C, Wang, Y, Fitzgerald KA, Underhill DM, Town T, Arditi M, Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis.  Immunity, 36 (3): 401-414, 2012
5. Shimada K, Crother TR, Karlin J, Chen S, Chiba N, Ramanujan VK, Vergnes L, Ojcius DM, Arditi M, Caspase-1 dependent IL-1b secretion is critical for host defense in a mouse model of Chlamydia pneumoniae lung infection.  PLoS ONE, 6 (6): e21477, 2011
6. Chiba N, Kakimoto K, Masuda A, and Matsuguchi T, Functional roles of Cot/Tpl2 in mast cell responses to lipopolysaccharide and FceRI-clustering.  Biochem Biophys Res Commun., 402 (1): 1-6, 2010
7. Kakimoto K, Musikacharoen T, Chiba N, et al., Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation.  J Physiol Biochem., 66 (1): 47-53, 2010
8. Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T, JNK activity is essential for ATF4 expression and late-stage osteoblast differentiation.  J Bone Mineral Res., 24 (3): 398-410, 2009
9. Chiba N, Masuda A, Yoshikai Y and Matsuguchi T,  Ceramide inhibits LPS-induced production of IL-5, IL-10, and IL-13 from mast cells.  J Cell Physiol.,  213 (1): 126-136, 2007

共同開発・研究

• 低出力超音波パルス（LIPUS）を用いた骨代謝制御（帝人ファーマ株式会社との共同研究）
• 力学的ストレスによる歯の移動メカニズム（本研究科歯科矯正学分野との共同研究）

主な研究費取得状況

松口徹也

大西智和

千葉紀香

分野サイト