田中 智之(教授) 藤井 正徳(准教授) 丹羽 里実(助教)

田中 智之(教授)

Researchmap: https://researchmap.jp/mast_cell1970/

ORCID: 0000-0002-3468-7694

最近の研究成果について

2019年

Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone. Yamada, K., Sato, H., Sakamaki, K., Kamada, M., Okuno, Y., Fukuishi, N., Furuta, K., Tanaka, S.Cells, 8, 12, 2019.

IgE非依存性のマスト細胞の活性化は、蕁麻疹、あるいは近年報告されている種々の慢性炎症性疾患の病態形成を考える上で重要であるが、適当な培養モデルがないために研究の進展は遅れていた。私たちは皮膚型マスト細胞の培養モデルを用いて、ポリカチオンやsubstance Pによるマスト細胞の脱顆粒応答がステロイド性抗炎症薬であるdexamethasoneによって抑制されることを明らかにした。これはマウスの耳介皮膚組織でも再現され、ステロイド性抗炎症薬の新たな作用機序のひとつであることが推察された。

2017年

1-Fluoro-2,4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells. Manabe, Y., Yoshimura, M., Sakamaki, K., Inoue, A., Kakinoki, A., Hokari, S., Sakanaka, M., Aoki, J., Miyachi, H., Furuta, K., and Tanaka, S. Eur. J. Immunol., 47, 60-67, 2017.

接触性皮膚炎のモデル抗原として用いられている1-Fluoro-2,4-dinitrobenzene (DNFB)が、ラットマスト細胞に直接作用し、脱顆粒応答を惹起することを明らかにした。このプロセスには、百日咳毒素感受性のGタンパク質共役型受容体が関与することを示唆した。一部の接触性皮膚炎においてマスト細胞が重要な役割を果たすことは報告されているが、抗原が直接マスト細胞を活性化する例は初めて示された。

2014年

Histamine synthesis is required for granule maturation of murine mast cells. Nakazawa, S., Sakanaka, M., Furuta, K., Natsuhara, M., Takano, H., Tsuchiya, S., Okuno, Y., Ohtsu, H., Nishibori, M., Thurmond, R. L., Hirasawa, N., Nakayama, K., Ichikawa, A., Sugimoto, Y., and Tanaka, S. Eur. J. Immunol. 44, 204-214, 2014.

ヒスチジン脱炭酸酵素(HDC)欠損マウスにおいて認められた組織マスト細胞の顆粒の形態学的異常が起こるメカニズムを検証した。マスト細胞自身が産生するヒスタミンが顆粒成熟の過程で必須であることが明らかとなったが、ヒスタミンの標的については既知の受容体ではない可能性が示唆された。高IgE血症はマスト細胞のヒスタミン合成を促進させるので、この過程でマスト細胞の成熟が促進され、さらにはアレルギー病態の増悪が起こるという可能性が考えられる。また、HDC阻害剤は慢性炎症に対するユニークな治療薬になるかもしれない。

本研究の背景と意義についての解説記事が同じ号で掲載された。Hallgren, J. and Gurish, M. F. Eur. J. Immunol. 44, 33-36, 2014.

原著論文

2019

Yamada, K., Sato, H., Sakamaki, K., Kamada, M., Okuno, Y., Fukuishi, N., Furuta, K., Tanaka, S.Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone. Cells, 8, 12 (2019)

Uchida, R., Egawa, T., Fujita, Y., Furuta, K., Taguchi, H., Tanaka, S., Nishida, K. Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation. Mol. Immunol., 105, 32-37 (2019)

2018

Kamei, M., Otani, Y., Hayashi, H., Nakamura, T., Yanai, K., Furuta, K., Tanaka, S. Suppression of IFN-γ production in murine splenocytes by histamine receptor antagonists. Int. J. Mol. Sci., 19, 4083 (2018)

Matsuo, Y., Yanase, Y., Irifuku, R., Takahagi, S., Mihara, S., Ishii, K., Kawaguchi, T., Tanaka, A., Iwamoto, K., Watanuki, H., Furuta, K., Tanaka, S., Inoue, A., Aoki, J., Hide, M. Neuromedin-U directly induces degranulation of skin mast cells, presumably via MRGPRX2. Allergy, 73, 2256-2260 (2018)

2017

Takeuchi, T., Harada, Y., Moriyama, S., Furuta, K., Tanaka, S., Miyaji, T., Omote, H., Moriyama, Y., and Hiasa, M. Vesicular polyamine transporter mediates vesicular storage and release of polyamine from mast cells. J. Biol. Chem., 292, 3909-3918 (2017)

Manabe, Y., Yoshimura, M., Sakamaki, K., Inoue, A., Kakinoki, A., Hokari, S., Sakanaka, M., Aoki, J., Miyachi, H., Furuta, K., and Tanaka, S. 1-Fluoro-2,4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells. Eur. J. Immunol., 47, 60-67 (2017)

2016

Hattori, M., Yamazaki, M., Ohashi, W., Tanaka, S., Hattori, K., Todoroki, K., Fujimori, T., Ohtsu, H., Matsuda, N., and Hattori, Y. Critical role of endogenous histamine in promoting end-organ tissue injury in sepsis.Intensive Care Med. Exp. (ICMx), 4, 36 (2016)

Sakanaka, M., Kurimune, Y., Yamada, K., Hyodo, N., Natsuhara, M., Ichikawa, A., Furuta, K., and Tanaka, S. Down-modulation of antigen-induced activation of murine cultured mast cells sensitized with a highly cytokinergic IgE clone. Immunol. Lett. 174, 1-8 (2016)

Oshikawa, Y., Furuta, K., Tanaka, S., and Ojida, A. Cell surface-anchored fluorescent probe capable of real-time imaging of single mast cell degranulation based on histamine-induced coordination displacement. Anal. Chem. 88, 1526-1529 (2016)

2014

Morimoto, K., Shirata, N., Taketomi, Y., Tsuchiya, S., Segi-Nishida, E., Inazumi, T., Kabashima, K., Tanaka, S., Murakami, M., Narumiya, S., and Sugimoto, Y. Prostaglandin E2-EP3 signaling induces inflammatory swelling by mast cell activation. J. Immunol. 192, 1130-1137 (2014)

Takeuchi, M., Sato, Y., Ohno, K., Tanaka, S., Takata, K., Gion, Y., Orita,Y., Ito, T., Tachibana, T. and Yoshino, T. T helper 2 and regulatory T cell cytokine production by mast cells: A key factor in the pathogenesis of IgG4-related disease. Mod. Pathol. 27, 1126-1136 (2014)

Taura, A., Furuta, K., Yamaguchi, T., Kawabata, K., and Tanaka, S. Regulation of histamine synthesis and tryptase expression through transcription factors, growth factor independent 1 (Gfi1) and Gfi1b, in murine cultured mast cells. Biol. Pharm. Bull. 37, 81-86 (2014)

Nakazawa, S., Sakanaka, M., Furuta, K., Natsuhara, M., Takano, H., Tsuchiya, S., Okuno, Y., Ohtsu, H., Nishibori, M., Thurmond, R. L., Hirasawa, N., Nakayama, K., Ichikawa, A., Sugimoto, Y., and Tanaka, S. Histamine synthesis is required for granule maturation of murine mast cells. Eur. J. Immunol. 44, 204-214 (2014)

2013

Taketomi, Y., Ueno, N., Kojima, T., Sato, H., Murase, R., Yamamoto, K., Tanaka, S., Sakanaka, M., Nakamura, M., Nishito, Y., Kawana, M., Kambe, N., Ikeda, K., Taguchi, R., Nakamizo, S., Kabashima, K., Gelb, M. H., Arita, M., Yokomizo, T., Nakamura, M., Watanabe, K., Hirai, H., Nakamura, M., Okayama, Y., Ra, C., Aritake, K., Urade, Y., Morimoto, K., Sugimoto, Y., Shimizu, T., Narumiya, S., Hara, S., Murakami, M. Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2–DP1 receptor paracrine axis. Nat. Immunol. 14, 554-563 (2013)

Kadota, Y., Sakai, N., Fujikawa, R., Aoyama, E., Zhong, M., Tanaka, S., and Gohda, E. Dextran sulfate-induced degradation of spontaneously apoptic B cells. Int. Immunopharmacol. 15, 581-587 (2013)

2012

Yamaguchi, T., Tashiro, K., Tanaka, S., Katayama, S., Ishida, W., Fukuda, K., Fukushima, A., Araki, R., Abe, M., Mizuguchi, H., and Kawabata, K. Two-step differentiation of mast cells from induced pluripotent stem cells. Stem Cells Dev., 22, 726-734 (2012)

Sugiura, Y., Hiramatsu, K., Hamauzu, R., Motoki, T., Miyazaki, M., Uto, H., Tsubouchi, H., Tanaka, S., and Gohda, E. Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymixin B. Cytokine 60, 205-211(2012)

Takano, H., Furuta, K., Yamashita, K., Sakanaka, M., Itano, N., Gohda, E., Nakayama, K., Kimata, K., Sugimoto, Y., Ichikawa, A., and Tanaka, S. Restriction of mast cell proliferation through hyaluronan synthesis by co-cultured fibroblasts. Biol. Pharm. Bull. 35, 408-412 (2012) Highlighted paper selected by Editor-in-Chief

2011

Ushio, H., Ueno, T., Kojima, Y., Komatsu, M., Tanaka, S., Yamamoto, A., Ichimura, Y., Ezaki, J., Nishida, K., Komazawa-Sakon, S., Niyonsaba, F., Ishi, T., Yanagawa, T., Kominami, E., Ogawa, H., Okumura, K., and Nakano, H. Crucial role for autophagy in degranulation of mast cells. J. Allergy Clin. Immunol. 127, 1267-1276 (2011)

2010

Goto, T., Sarker, M. M. R., Zhong, M., Tanaka, S., and Gohda, E. Enhancement of IgM production in B cells by the extract of red bell pepper. J. Health Sci. 56, 304-309 (2010)

Sakanaka, M., Furuta, K., Ichikawa, A., and Tanaka, S. Impaired activation of mast cells upon IgE-mediated antigen stimulation in a stroke-prone spontaneously hypertensive rat strain, SHRSP.Z Immunol. Lett. 128, 74-79 (2010)

Matsuura, J., Sakanaka, M., Sato, N., Ichikawa, A., and Tanaka, S. Suppression of CXCR4 expression in mast cells upon IgE-mediated antigen stimulation. Inflamm. Res. 59, 123-127, (2010)

2009

Yamaoka, K., Yano, A., Kuroiwa, K., Morimoto, K., Inazumi, T., Hatae, N., Tabata, H., Segi-Nishida, E., Tanaka, S., Ichikawa, A., and Sugimoto, Y. Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner. Biochem. Biophys. Res. Commun. 389, 678-682 (2009)

Sato, N., Tanaka, S.*, Matsuura, J., Takasu, Y., and Ichikawa, A. Interleukin-4-mediated suppression of histamine synthesis in a murine mast cell line, BNu-2cl3. Biol. Pharm. Bull. 32, 1800-1802 (2009)

Tsuchiya, S., Tachida, Y., Segi-Nishida, E., Okuno, Y., Tamba, S., Tsujimoto, G., Tanaka, S., and Sugimoto, Y. Characterization of gene expression profiles for different types of mast cells pooled from mouse stomach subregions by an RNA amplification method. BMC Genomics 10, 35 (2009)

Takano, H., Nakazawa, S., Shirata, N., Tamba, S., Furuta, K., Tsuchiya, S., Morimoto, K., Itano, N., Irie, A., Kimata, K., Nakayama, K., Sugimoto, Y., and Tanaka, S. Involvement of CD44 in mast cell proliferation during terminal differentiation. Lab. Invest. 89, 446-455 (2009)

2008

Sakanaka, M., Tanaka, S.*, Sugimoto, Y., and Ichikawa, A. Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix. Am. J. Physiol. Cell Physiol. 295, C1427-C1433 (2008)

Takano, H., Nakazawa, S., Okuno, Y., Shirata, N., Tsuchiya, S., Kainoh, T., Takamatsu, S., Furuta, K., Taketomi, Y., Naito, Y., Takematsu, H., Kozutsumi, Y., Tsujimoto, G., Murakami, M., Kudo, I., Ichikawa, A., Nakayama, K., Sugimoto, Y., and Tanaka, S. Establishment of the culture model system that reflects the process of terminal differentiation of connective tissue-type mast cells. FEBS Lett. 582, 1444-1450 (2008)

Kataoka, H., Sakanaka, M., Semma, M., Yamamoto, T., Hirota, S., Tanaka, S.*, and Ichikawa, A. PGE2-receptor subtype EP4-dependent adherence of mastocytoma P-815 cells to matrix components in subcutaneous tissues overlaying inside surface of air pouch cavity in CDF1 mouse. Inflamm. Res. 57, 362-366 (2008)

2007

Ueta, M., Nakamura, T., Tanaka, S., Kojima, K., and Kinoshita, S. Development of eosinophilic conjunctival inflammation at late-phase reaction in mast cell-deficient mice. J. Allergy Clin. Immunol. 120, 476-478 (2007)

Taketomi, Y., Sunaga, K., Tanaka, S., Nakamura, M., Arata, S., Okuda, T., Moon, T., Chang, H., Sugimoto, Y., Kokame, K., Miyata, T., Murakami, M., and Kudo, I. Impaired mast cell maturation and degranulation and attenuated allergic responses in NDRG1-deficient mice. J. Immunol. 178, 7042-7053 (2007)

Furuta, K., Nakayama, K., Sugimoto, Y., Ichikawa, A., and Tanaka, S. Activation of histidine decarboxylase through post-translational cleavage by caspase-9 in a mouse mastocytoma P-815. J. Biol. Chem. 282, 13438-13446 (2007)

2006

Furuta, K., Ichikawa, A., Nakayama, K., and Tanaka, S. Membrane orientation of the precursor 74-kDa form of L-histidine decarboxylase. Inflamm. Res. 55, 185-191 (2006)

2005

Liu, Y., Furuta, K., Teshima, R., Shirata, N., Sugimoto, Y., Ichikawa, A., and Tanaka, S. Critical role of PKCβII in activation of mast cells by monomeric IgE. J. Biol. Chem. 280, 38976-38981 (2005)

Sugimoto, Y., Fukada, Y., Mori, D., Tanaka, S., Yamane, H., Okuno, Y., Deai, K., Tsuchiya, S., Tsujimoto, G., and Ichikawa, A. Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via the prostanoid EP2 receptor in mouse peritoneal neutrophils. J. Immunol. 175, 2606-2612. (2005)

Kunikata, T., Yamane, H., Segi, E., Matsuoka, T., Sugimoto, Y., Tanaka, S., Tanaka, H., Nagai, H., Ichikawa, A., and Narumiya, S. Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Nat. Immunol. 6, 524-531. (2005)

Tanaka, S., Mikura, S., Hashimoto, E., Sugimoto, Y., and Ichikawa, A. Ca2+ influx-mediated histamine synthesis and IL-6 release in mast cells activated by monomeric IgE. Eur. J. Immunol. 35, 460-468 (2005)

2004

Nakamura, E., Kataoka, T., Furutani, K., Jimbo, K., Aihara, T., Tanaka, S., Ichikawa, A., Ohtsu, H., and Okabe, S. Lack of histamine alters gastric mucosal morphology: Comparison between histidine decarboxylase-deficient and mast cell-deficient mice. Am. J. Physiol.-Gastrointest. Liver. Physiol. 287, G1053-1061 (2004)

Kawazoe, Y., Tanaka, S., and Uesugi, M. Chemical genetic identification of the histamine H1 receptor as a stimulator of insulin-induced adipogenesis. Chem. Biol. 11, 907-913 (2004)

Tanaka, S., Deai, K., Konomi, A., Takahashi, K., Yamane, H., Sugimoto, Y., and Ichikawa, A. Expression of L-histidine decarboxylase in granules of elicited mouse polymorphonuclear leukocytes. Eur. J. Immunol. 34, 1472-1482 (2004)

Sugimoto, Y., Nakato, T., Kita, A., Takahashi, Y., Hatae, N., Tabata, H., Tanaka, S., and Ichikawa, A. A cluster of aromatic amino acids in the i2 loop plays a key role for Gs coupling in prostaglandin EP2 and EP3 receptors. J. Biol. Chem. 279, 11016-11026. (2004).

2003

Sugimoto, Y., Nakato, T., Kita, A., Hatae, N., Tabata, H., Tanaka, S., and Ichikawa, A. Functional domains essential for Gs activity in prostaglandin EP2 and EP3 receptors. Life Sci. 74, 135-141. (2003)

Tsuchiya, S., Tanaka, S., Sugimoto, Y., Katsuyama, M., Ikegami, R., and Ichikawa, A. Identification and characterization of a novel progesterone receptor-binding element in the mouse prostaglandin E receptor subtype EP2 gene. Genes Cells 8, 747-758. (2003)

Wagner, W., Ichikawa, A., Tanaka, S., Panula, P., and Fogel, W. A. Mouse mammary epithelial histamine system. J. Physiol. Pharmacol. 54, 211-223 (2003).

Furutani, K., Aihara, T., Nakamura, E., Tanaka, S., Ichikawa, A., Ohtsu, H., and Okabe, S. Crucial role of histamine for regulation of gastric acid secretion ascertained by histidine decarboxylase-knockout mice. J. Pharmacol. Exp. Ther. 307, 331-338 (2003).

Tanaka, S., Deai, K., Inagaki, M., and Ichikawa, A. Uptake of histamine by mouse peritoneal macrophages and a macrophage cell line, RAW264.7. Am. J. Physiol.-Cell Physiol. 285, C592-C598 (2003).

Hunyady, B., Zolyomi, A., Czimmer, J., Mozsik, G., Kozixz, T., Buzas, E., Tanaka, S., Ichikawa, A., Nagy, A., Palkovits, M., and Falus, A. Expanded parietal cell pool in transgenic mice unable to synthesize histamine. Scand. J. Gastroenterol. 38 (2), 133-140 (2003).

Wagner, W., Tanaka, S., Ichikawa, A., and Fogel, W. A. Phosphorothioate antisense oligodeoxynucleotides against histidine decarboxylase: a study in mouse mammary epithelial cell cultures. Inflamm. Res. 52 (suppl 1), S59-S62 (2003).

Hatae, N., Kita, A., Tanaka, S., Sugimoto, Y., and Ichikawa, A. Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two PGE2 receptor subtypes, EP3 and EP4. J. Biol. Chem. 278, 17977-17981 (2003)

Segi, E., Haraguchi, K., Sugimoto, Y., Tsuji, M., Tsunekawa, H., Tamba, S., Tsuboi, K., Tanaka, S., and Ichikawa, A. Expression of messenger RNA for prostaglandin E receptor subtypes EP4/EP2 and cyclooxygenase isozymes in mouse periovulatory follicles and oviducts during superovulation. Biol. Reprod. 68, 804-811. (2003)

2002

Tabata, H., Tanaka, S., Sugimoto, Y., Kanki, H., Kaneko, S., and Ichikawa, A. Possible coupling of prostaglandin E receptor EP1 to TRP5 expressed in X. laevis oocytes. Biochem. Biophys. Res. Commun. 298, 398-402. (2002)

Takahashi, K., Tanaka, S., Furuta, K., and Ichikawa, A. Histamine H2 receptor-mediated modulation of local cytokine expression in a mouse experimental tumor model. Biochem. Biophys. Res. Commun. 297, 1205-1210 (2002).

Tanaka, S., Takasu, Y., Mikura, S., Satoh, N., and Ichikawa, A. Antigen-independent induction of histamine synthesis by immunoglobulin E in mouse bone marrow derived mast cells. J. Exp. Med. 196, 229-235 (2002).

Ohtsu, H., Kuramasu, A., Tanaka, S., Terui, T., Hirasawa, N., Hara, M., Makabe-Kobayashi, Y., Yamada, N., Yanai, K., Sakurai, E., Okada, M., Ohuchi, K., Ichikawa, A., Nagy, A., and Watanabe, T. Plasma extravasation induced by dietary supplemented histamine in histamine-free mice. Eur. J. Immunol. 32, 1698-1708 (2002)

Safina, F., Tanaka, S., Inagaki, M., Tsuboi, K., Sugimoto, Y., and Ichikawa, A. Expression of L-histidine decarboxylase in mouse male germ cells. J. Biol. Chem. 277, 14211-14215 (2002)

Tanaka, S., Hamada, K., Yamada, N., Sugita, Y., Tonai, S., Hunyady, B., Palkovits, M., Falus, A., Watanabe, T., Okabe, S., Ohtsu, H., Ichikawa, A., and Nagy, A. Gastric acid secretion in L-histidine decarboxylase deficient mice. Gastroenterology 122, 145-155 (2002)

Tanaka, S., Konomi, A., Takahashi, K., and Ichikawa, A. Histamine synthesis in mouse polymorphonuclear neutrophils. Inflamm. Res. 51 (suppl1), S17-S18 (2002)

2001

Ohtsu, H., Tanaka, S., Terui, T., Hori, Y., Makabe-Kobayashi, Y., Pejler, G., Tchougounova, E., Hellman, L., Gertsenstein, M., Hirasawa, N., Sakurai, E., Buzas, E., Kovacs, P., Csaba, G., Kittel, A., Okada, M., Hara, M., Mar, L., Numayama-Tsuruta, K., Ishigaki-Suzuki, S., Ohuchi, K., Ichikawa, A., Falus, A., Watanabe, T., and Nagy, A. Mice lacking histidine decarboxylase exhibit abnormal mast cells. FEBS Lett. 502, 53-56 (2001)

Tanaka, S., and Ichikawa, A. Intracellular localization of histidine decarboxylase. Inflamm. Res. 50 (suppl2), S98-S99 (2001)

Takahashi, K,. Tanaka, S., and Ichikawa, A. Effect of cimetidine on intratumoral cytokine expression in an experimental tumor. Biochem. Biophys. Res. Commun. 281(5), 1113-1119 (2001)

2000

Yamane, H., Sugimoto, Y., Tanaka, S., and Ichikawa, A. Prostaglandin E2 receptor, EP2 and EP4, differentially modulate TNF-α and IL-6 production induced by lipopolysuccharide in mouse peritoneal neutrophils. Biochem. Biophys. Res. Commun. 278, 224-228. (2000)

1998

Suzuki, S., Tanaka, S., Nemoto, K., and Ichikawa, A. Membrane targeting and binding of the 74 kDa form of mouse L-histidine decarboxylase via its carboxyl-terminal sequence. FEBS Lett. 437, 44-48. (1998)

Tanaka, S., Nemoto, K., Yamamura, E., and Ichikawa, A. Intracellular localization of the 74- and 53- kDa forms of L-histidine decarboxylase in a rat basophilic/mast cell line, RBL-2H3.J. Biol. Chem. 273, 8177-8182. (1998)

Ichikawa, A., Funakoshi, E., Tanaka, S., Nemoto, K., and Fukui, T. Benzamidine-sensitive proteinase in activated cleavage of recombinant 74 kDa histidine decarboxylase into its 53 kDa form in mastocytoma cells. Inflamm. Res. 47, suppl 1, S46-S47. (1998)

1997

Tanaka, S., Nemoto, K., Yamamura, E., Ohmura, S., and Ichikawa, A. Degradation of the 74 kDa form of L-histidine decarboxylase via the ubiquitin-proteasome pathway in a rat basophilic/mast cell line (RBL-2H3). FEBS Lett. 417, 203-207. (1997)

Nakagawa, S., Okaya, Y., Yatsunami, K., Tanaka, S., Ohtsu, H., Fukui, T., Watanabe, T., and Ichikawa, A. Identification of multiple regulatory elements of human L-histidine decarboxylase gene. J. Biochem. 121, 935-940. (1997)

1996

Ohtsu, H., Kuramasu, A., Suzuki, S., Igarashi, K., Ohuchi, Y., Sato, M., Tanaka, S., Nakagawa, S., Shirato, K., Yamamoto, M., Ichikawa, A., and Watanabe, T. Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. J. Biol. Chem. 271, 28439-28444. (1996)

Asahara, M., Mushiake, S., Shimada, S., Fukui, H., Kinoshita, Y., Kawanami, C., Watanabe, T., Tanaka, S., Ichikawa, A., Uchiyama, Y., Narushima, Y. Takasawa, S., Okamato, H., Tohyama, M., and Chiba, T. Reg gene expression is increased in rat gastric enterochromaffin-like cells following water immersion stress. Gastroenterology. 111, 45-55. (1996)

1995

Tanaka, S., Funakoshi, E., Kawahara, A., Nemoto, K., Fukui, T., Suzuki, T., Igarashi, K., and Ichikawa, A. Effect of repeated cold stress on mouse stomach histidine decarboxylase.Meth. Find. Exp. Clin. Pharmacol. 17(C), 25-29. (1995)

Ichikawa, A., Fukui, T., Yamamoto, J., Ohgoh, M., Tanaka, S., and Funakoshi, E. De novo synthesis and posttranslational processing of L-histidine decarboxylase in mice. Meth. Find. Exp. Clin. Pharmacol. 17(C), 5-9. (1995)

Tanaka, S., Fukui, T., Yamamoto, J., Shima, Y., Kume, T., Ohgo, M and Ichikawa, A. Processing and activation of recombinant mouse mastocytoma histidine decarboxylase in the particulate fraction of Sf9 cells by porcine pancreatic elastase. Biochim. Biophys. Acta. 1253, 9-12. (1995)

1993

Yamamoto, J., Fukui, T., Suzuki, K., Tanaka, S., Yatsunami, K., and Ichikawa, A. Expression and characterization of recombinant mouse mastocytoma histidine decarboxylase. Biochim. Biophys. Acta. 1216, 431-440. (1993)

総説

Ichikawa, A., Sugimoto, Y., and Tanaka, S. Molecular Biology of Histidine Decarboxylase and Prostaglandin Receptors. Proc. Jpn. Acad., Ser. B 86, 848-866 (2010)

Tanaka, S. Targeting CD44 in mast cell regulation. Expert Opin. Ther. Targets 14 (1), 31-43 (2010)

Tanaka, S., and Ichikawa, A. Immune regulatory roles of histamine produced by leukocytes. J. Pharmacol. Sci. 101, 19-23 (2006)

日本語記事

田中 智之:Histamineと掻痒:臨床免疫・アレルギー科 69 (4), 342-347, 2018

田中 智之:研究公正を目指す取り組み:現状と新しい動き:薬学雑誌 138 (4), 477-486, 2018

田中 智之:誠実な研究活動のために(Part 2):ファルマシア 52(4), 317-321, 2016

田中 智之:誠実な研究活動のために(Part 1):ファルマシア 52(2), 131-135, 2016

田中 智之:創薬の標的としてのマスト細胞:MEDCHEM NEWS 24巻、33-38 (2014)

田中 智之、古田 和幸:ヒスタミンとアナフィラキシー:アレルギー・免疫 20巻、50-54 (2013)

田中 智之、西田 圭吾:マスト細胞研究の新たな展開:薬学雑誌 131巻、59-61 (2011)

田中 智之:皮膚型マスト細胞モデルの確立とその解析:薬学雑誌 131巻、63-71 (2011)

田中 智之:マスト細胞の分化に伴う機能制御(日本生化学会奨励賞総説):生化学 第82巻、1021-1032 (2010)

田中 智之:マスト細胞の成熟とヒアルロン酸:表面 45巻、312-321 (2007)

田中 智之:IgEを介するマスト細胞活性化の多様性、特集「マスト細胞の活性化をめぐって」:臨床免疫・アレルギー科 47巻、421-426 (2007)

田中 智之:マスト細胞におけるIgEを介したヒスタミン合成の誘導機構、特集「アレルギー性炎症反応におけるヒスタミンの役割と抗ヒスタミン薬」:アレルギー科 21巻、438-444 (2006)

田中 智之:単量体IgEによるマスト細胞の活性化、特集「アレルギー疾患におけるマスト細胞の位置づけ」(編集・羅 智靖):アレルギー・免疫 13 (6), 50-56 (2006)

田中 智之:ヒスタミン生合成を介して発現する生理機能の解析(日本薬学会奨励賞受賞記念総説):薬学雑誌 123 (7), 547-559 (2003).

田中 智之:新たな抗アレルギー薬の標的?ヒスタミン H4 受容体の発見:ファルマシア 38 (1), 64-65 (2002)

田中 智之、市川 厚:ヒスタミン生合成の分子機構「ヒスタミン研究の最近の進歩」別冊・医学のあゆみ(医歯薬出版)(2000)

田中 智之:SRP 非依存的な小胞体へのタンパク質輸送:生化学 72 (2), 121-125 (2000)

市川 厚、田中 智之:ヒスチジン脱炭酸酵素の分子生物学:医学のあゆみ 188 (3), 163-167 (1999)

著書・訳書

科学者の研究倫理 化学・ライフサイエンスを中心に」田中智之、小出隆規、安井裕之 東京化学同人(2018年)

「薬学研究(スタンダード薬学シリーズⅡ)」日本薬学会(編)東京化学同人(2017年):第Ⅰ部「研究の心構え」

「図解 薬学・副作用学(改訂2版)」 川西正祐、小野秀樹、賀川義之(編)南山堂(2017年):「薬物アレルギー」

「キャンベルファーレル生化学」 川嵜敏祐、金田典雄(監訳)廣川書店(2011年):14章「ウイルス、がん、免疫学」翻訳

「わかりやすい免疫学」 市川厚・田中智之(編著)廣川書店(2008年)

Regulation of mammalian histamine synthesis: histidine decarboxylase. Tanaka, S. and Ichikawa, A. in “Biomedical Aspects of Histamine: Current Perspectives” (ed. Khardori, N., Shahid, M., Khan, RA, and Tripathi, T, Springer)

その他

田中 智之「ダメな統計学 悲惨なほど完全なる手引書」(書評)ファルマシア 53, 12, 1207 (2017)

Tanaka, S. and Ichikawa, A. Histamine biosynthesis and function. eLS (Encyclopedia of Life Science, WILEY) (2012)

田中 智之:組織環境におけるマスト細胞の新たな機能(最近の話題):日薬理誌 138, 301 (2011)

田中 智之:網羅的ゲノムスクリーニングによる新たな薬物の標的探索法の開発(注目の論文):化学 59 (11), 60-61 (2004)

藤井 正徳(准教授)

Research map: https://researchmap.jp/read0199800/

ORCID: 0000-0003-2050-4567

原著論文

*corresponding author

2019

Fujii M.*, Ohgami S., Asano E., Nakayama T., Toda T., Nabe T., Ohya S. Brain allopregnanolone induces marked scratching behaviour in diet-induced atopic dermatitis mouse model. Sci. Rep., 9, 2364 (2019)

2018

Fujii M.*, Takeuchi K., Umehara Y., Takeuchi M., Nakayama T., Ohgami S., Asano E., Nabe T., Ohya S. Barbiturates enhance itch-associated scratching in atopic dermatitis mice: A possible clue to understanding nocturnal pruritus in atopic dermatitis. Eur. J. Pharmacol., 836, 57–66 (2018)

Follansbee T., Akiyama T., Fujii M., Davoodi A., Nagamine M., Carstens M.I., Carstens E*. Effects of pruritogens and algogens on rostral ventromedial medullary (RVM) ON and OFF cells. J. Neurophysiol., 120, 2156–2163 (2018)

Khatun A., Shimozawa M., Kito H., Kawaguchi M., Fujimoto M., Ri M., Kajikuri J., Niwa S., Fujii M., Ohya S*. Transcriptional Repression and Protein Degradation of the Ca2+-Activated K+ Channel KCa1.1 by Androgen Receptor Inhibition in Human Breast Cancer Cells. Front. Physiol., 9, 312 (2018)

Fujii M.*, Ohyanagi C., Kawaguchi N., Matsuda H., Miyamoto Y., Ohya S., Nabe T. Eicosapentaenoic acid ethyl ester ameliorates atopic dermatitis-like symptoms in special diet-fed hairless mice, partly by restoring covalently bound ceramides in the stratum corneum. Exp. Dermatol., 27, 837–840 (2018)

2016

Tagishi K., Shimizu A., Endo K., Kito H., Niwa S., Fujii M., Ohya S*. Defective splicing of the background K+ channel K2P5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4+ T cells. J. Pharmacol. Sci., 132, 205–209 (2016)

Fujii M.*, Endo-Okuno F., Iwai A., Doi K., Tomozawa J., Kohno S., Inagaki N., Nabe T., Ohya S. Hypomorphic mutation in the hairless gene accelerates pruritic atopic skin caused by feeding a special diet to mice. Exp. Dermatol., 25, 565–567 (2016)

2015

Nakakura S., Matsui M., Sato A., Ishii M., Endo K., Muragishi S., Murase M., Kito H., Niguma H., Kurokawa N., Fujii M., Araki M., Araki K., Ohya S*. Pathophysiological significance of the two-pore domain K+ channel K2P5.1 in splenic CD4+CD25- T cell subset from a chemically-induced murine inflammatory bowel disease model. Front. Physiol., 6, 299 (2015)

Endo K., Kurokawa N., Kito H., Nakakura S., Fujii M., Ohya S*. Molecular identification of the dominant-negative, splicing isoform of the two-pore domain K+ channel K2P5.1 in lymphoid cells and enhancement of its expression by splicing inhibition. Biochem. Pharmacol., 98, 440–452 (2015)

Sekioka T., Kadode M., Fujii M., Kawabata K., Abe T., Horiba M., Kohno S., Nabe T*. Expression of CysLT2 receptors in asthma lung, and their possible role in bronchoconstriction. Allergol. Int., 64, 351–358 (2015)

Fujii M.*, Shimazaki Y., Muto Y., Kohno S., Ohya S., Nabe T. Dietary deficiencies of unsaturated fatty acids and starch cause atopic dermatitis-like pruritus in hairless mice. Exp. Dermatol., 24, 108–113 (2015)

2014

Matsuba S., Niwa S., Muraki K., Kanatsuka S., Nakazono Y., Hatano N., Fujii M., Zhan P., Suzuki T., Ohya S*. Downregulation of Ca2+-activated Cl- channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells. J. Pharmacol. Exp. Ther., 351, 510–518 (2014)

Ohya S.*, Fukuyo Y., Kito H., Shibaoka R., Matsui M., Niguma H., Maeda Y., Yamamura H., Fujii M., Kimura K., Imaizumi Y. Upregulation of KCa3.1 K+ channel in mesenteric lymph node CD4+ T lymphocytes from a mouse model of dextran sulfate-induced inflammatory bowel disease. Am. J. Physiol. Gastrointest. Liver physiol., 306, G873–G885 (2014)

2013

Nabe T.*, Kijitani Y., Kitagawa Y., Sakano E., Ueno T., Fujii M., Nakao S., Sakai M., Takai S. Involvement of chymase in allergic conjunctivitis of guinea pigs. Exp. Eye Res., 113, 74–79 (2013)

Fujii M.*, Nakashima H., Tomozawa J., Shimazaki Y., Ohyanagi C., Kawaguchi N., Ohya S., Kohno S., Nabe T. Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice. Exp. Dermatol., 22, 272–277 (2013)

Nabe T.*, Matsuya K., Akamizu K., Fujita M., Nakagawa T., Shioe M., Kida H., Takiguchi A., Wakamori H., Fujii M., Ishihara K., Akiba S., Mizutani N., Yoshino S., Chaplin D.D. Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice. Br. J. Pharmacol., 169, 462–476 (2013)

Cao Y., Fujii M., Ishihara K., Akiba S., Yasui H., Nabe T.* Effect of a peroxynitrite scavenger, a manganese-porphyrin compound in airway remodeling in a murine asthma. Biol. Pharm. Bull., 36, 850–855 (2013)

2012

Nabe T.*, Ikedo A., Hosokawa F., Kishima M., Fujii M., Mizutani N., Yoshino S., Ishihara K., Akiba S., Chaplin D.D. Regulatory role of antigen-induced interleukin-10, produced by CD4(+) T cells, in airway neutrophilia in a murine model for asthma. Eur. J. Pharmacol., 677, 154–162 (2012)

2011

Fujii M., Shimizu T., Nakamura T., Endo F., Kohno S., Nabe T.* Inhibitory effect of chitosan-containing lotion on scratching response of hairless mice with atopic dermatitis-like dry skin. Biol. Pharm. Bull., 34, 1890–1894 (2011)

Nabe T.*, Morishita T., Matsuya K., Ikedo A., Fujii M., Mizutani N., Yoshino S. Complete dependence on CD4+ cells in late asthmatic response, but limited contribution of the cells to airway remodeling in sensitized mice. J. Pharmacol. Sci., 116, 373–383 (2011)

Nabe T.*, Kuriyama Y., Mizutani N., Shibayama S., Hiromoto A., Fujii M., Tanaka K., Kohno S. Inhibition of hematopoietic prostaglandin D synthase improves allergic nasal blockage in guinea pigs. Prostaglandins Other Lipid Mediat., 95, 27–34 (2011)

Nabe T.*, Hosokawa F., Matsuya K., Morishita T., Ikedo A., Fujii M., Mizutani N., Yoshino S., Chaplin D.D. Important role of neutrophils in the late asthmatic response in mice. Life Sci., 88, 1127–1135 (2011)

2009

Fujii M., Nakamura T., Fukuno S., Mizutani N., Nabe T.*, Kohno S. Ethanol aggravates itch-related scratching in hairless mice developing atopic dermatitis. Eur. J. Pharmacol., 611, 92–99 (2009)

Ogita-Nakanishi H., Nabe T.*, Mizutani N., Fujii M., Kohno S. Absence of nasal blockage in a Japanese ceder pollen-induced allergic rhinitis model mouse. Allergol. Int., 58, 171–178 (2009)

Nabe T.*, Tsuzuike N., Ohtani Y., Mizutani N., Watanabe S., Fujii M., Yoshimura M., Nagasawa M., Kohno S. Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs. Clin. Exp. Allergy, 39, 138–146 (2009)

2008

Nabe T.*, Kubota K., Mizutani N., Fujii M., Terada T., Takenaka H., Kohno S. Effect of local nasal immunotherapy on nasal blockage in pollen-induced allergic rhinitis of guinea pigs. Allergol. Int., 57, 419–427 (2008)

Nagata T., Nabe T.*, Fujii M., Mizutani N., Kohno S. Effects of multiple dexamethasone treatments on aggravation of allergic conjunctivitis associated with mast cell hyperplasia. Biol. Pharm. Bull., 31, 464–468 (2008)

Mizutani N., Nabe T.*, Fujii M., Yoshino S., Kohno S. Involvement of peroxynitrite in pollen-induced nasal blockage in guinea pigs. Eur. J. Pharmacol., 582, 139–144 (2008)

2007

Mizutani N., Nabe T.*, Ohtani Y., Han H.Y., Fujii M., Yoshino S., Hirayama T., Kohno S. Polycyclic aromatic hydrocarbons aggravate antigen-induced nasal blockage in experimental allergic rhinitis. J. Pharmacol. Sci., 105, 291–297 (2007)

Han H.Y., Nabe T.*, Mizutani N., Fujii M., Terada T., Takenaka H., Kohno S. Nasal blockage induced by oral administration of Non-steroidal anti-inflammatory drugs in a guinea-pig model of allergic rhinitis. J. Pharmacol. Sci., 105, 251–257 (2007)

Fujii M., Akita K., Mizutani N., Nabe T., Kohno S*. Development of numerous nerve fibers in the epidermis of hairless mice with atopic dermatitis-like pruritic skin inflammation. J. Pharmacol. Sci., 104, 243–251 (2007)

2006

Tanaka Y., Mizutani N., Fujii M., Nabe T., Kohno S.* Different mechanisms between thromboxane A2- and leukotriene D4-induced nasal blockage in guinea pigs. Prostaglandins Other Lipid Mediat., 80, 144–154 (2006)

Matsumura D., Nabe T., Mizutani N., Fujii M., Kohno S.* Detection of new antigenic proteins in Japanese ceder pollen. Biol. Pharm. Bull., 29, 1162–1166 (2006)

Fujii M., Nabe T., Tomozawa J., Kohno S.* Involvement of skin barrier dysfunction in itch-related scratching in special diet-fed hairless mice. Eur. J. Pharmacol., 530, 152–156 (2006)

2005

Katayama G., Nabe T., Fujii M., Kohno S.* Mast cell hyperplasia induced by multiple challenge with ceder pollen in sensitized guinea pigs. Inflamm. Res., 54, 370–374 (2005)

Fujii M., Tomozawa J., Mizutani N., Nabe T., Danno K., Kohno S.* Atopic dermatitis-like pruritic skin inflammation caused by feeding a special diet to HR-1 hairless mice. Exp. Dermatol., 14, 460–468 (2005)

2003

Fuchibe K., Nabe T, Fujii M, Mizutani N, Danno K, Koda A, Kohno S.* Delayed type allergic itch-associated response induced by toluene-2,4-diisocyanate in hairless mice. J. Pharmacol. Sci., 93, 47–54 (2003)

総説

Fujii M., Kohno S., Nabe T. Atopic dermatitis model of itching behavior in hairless mice. Inflammation and Regeneration, 30, 434–439 (2010)

日本語記事

藤井 正徳 : 飲酒と痒み.Journal of Visual Dermatology, 16, 1089 (2017)

藤井 正徳 : ヘアレスマウスにおける食餌誘発アトピー性皮膚炎の発症要因の解明. (平成27年度日本薬学会近畿支部奨励賞総説) YAKUGAKU ZASSHI, 137, 49–54 (2017)

藤井 正徳 : 新しい痒み研究のマウスモデル. アレルギー・免疫, 23, 30-36 (2016)

藤井 正徳 : 食餌誘発アトピー性皮膚炎モデルの病態解析. BIO Clinica, 31, 92-97 (2016)

藤井 正徳 : Mas関連Gタンパク質共役受容体と痒み. 日本薬理学雑誌, 145, 219 (2015)

藤井 正徳 : ピーナッツによるアナフィラキシーには補体の活性化が関与する. ファルマシア, 45(9), 919–920 (2009)

河野 茂勝,藤井 正徳,奈邉 健. 新しい痒みのモデルとその解析. 臨床免疫・アレルギー科, 48, 152–157 (2007)

丹羽 里実(助教)

2018

Khatun A, Shimozawa M, Kito H, Kawaguchi M, Fujimoto M, Ri M, Kajikuri J, Niwa S, Fujii M, Ohya S. Transcriptional Repression and Protein Degradation of the Ca2+-Activated K+ Channel KCa1.1 by Androgen Receptor Inhibition in Human Breast Cancer Cells. Front. Physiol., (2018)

2017

Fujimoto M, Inoue T, Kito H, Niwa S, Suzuki T, Muraki K, Ohya S. Transcriptional repression of HER2 by ANO1 Cl- channel inhibition in human breast cancer cells with resistance to trastuzumab. Biochem. Biophys. Res. Commun., 482, 188-194 (2017)

2016

Khatun A, Fujimoto M, Kito H, Niwa S, Suzuki T, Ohya S. Down-Regulation of Ca2+-Activated K⁺ Channel KCa1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists. Int. J. Mol. Sci., E2083 (2016)

Tagishi K, Shimizu A, Endo K, Kito H, Niwa S, Fujii M, Ohya S. Defective splicing of the background K+ channel K2P5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4+ T cells. J. Pharmacol. Sci., 132, 205-209 (2016)

Ohya S, Kanatsuka S, Hatano N, Kito H, Matsui A, Fujimoto M, Matsuba S, Niwa S, Zhan P, Suzuki T, Muraki K. Downregulation of the Ca(2+)-activated K(+) channel KC a3.1 by histone deacetylase inhibition in human breast cancer cells. Pharmacol. Res. Perspect. 4, e00228 (2016)

2014

Matsuba S, Niwa S, Muraki K, Kanatsuka S, Nakazono Y, Hatano N, Fujii M, Zhan P, Suzuki T, Ohya S. Downregulation of Ca2+-activated Cl- channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells. J. Pharmacol. Exp. Ther. 351, 510-518, 2014

2012

Niwa S, Ohya S, Kojima Y, Sasaki S, Yamamura H, Sakuragi M, Kohri K, Imaizumi Y. Down-regulation of the large-conductance Ca(2+)-activated K+ channel, K(Ca)1.1 in the prostatic stromal cells of benign prostate hyperpolasia. Biol. Pharm. Bull. 35, 737-744, 2012.

2011

Ohya S, Niwa S, Kojima Y, Sasaki S, Sakuragi M, Kohri K, Imaizumi Y. Intermediate-conductance Ca2+-activated K+ channel, KCa3.1, as a novel therapeutic target for benign prostatic hyperplasia. J. Pharmacol. Exp. Ther. 338, 528-536, 2011.

Ohya S, Niwa S, Yanagi A, Fukuyo Y, Yamamura H, Imaizumi Y. Involvement of dominant-negative spliced variants of the intermediate conductance Ca2+-activated K+ channel, K(Ca)3.1, in immune function of lymphoid cells. J. Biol. Chem. 286, 16940-16952, 2011.

2009

Ohya S, Kimura K, Niwa S, Ohno A, Kojima Y, Sasaki S, Kohri K, Imaizumi Y. Malignancy grade-dependent expression of K+-channel subtypes in human prostate cancer. J. Pharmacol. Sci. 109, 148-151, 2009.

 

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