研究テーマ
アレルギーおよび自己免疫疾患の病態解析と免疫薬理学的制御
花粉症、気管支喘息、アトピー性皮膚炎、食物アレルギーなどのアレルギー疾患および関節リウマチなどの自己免疫疾患では、種々の抗原（アレルゲン・自己抗原）に対する抗体が重要な役割を果たしているため、本研究室ではこれら抗原に対するモノクローナル抗体を独自に作製し、これら抗体によって誘導されるアレルギー疾患および自己免疫性関節炎モデルをマウスにおいて確立しました。現在、これらモデルの病態解析を行うとともに、これら疾患の免疫薬理学的制御を試みています。
スタッフ
小山 豊 教授
担当科目：薬理学Ⅲ、薬理学Ⅳ、薬理学実習、病態薬理生化学特論（大学院）、病態解析治療学特論（大学院）
八巻 耕也 准教授
担当科目：薬理学I、医薬品毒性学、薬理学実習、病態薬理生化学特論（大学院）、病態解析治療学特論（大学院）
学位：薬学博士
泉 安彦 講師
担当科目：薬理学Ⅱ、薬理学Ⅳ、医薬品毒性学、薬理学実習、病態薬理生化学特論（大学院）
学位：博士（薬学）
研究成果
2021
Koyama Y*, Tsuboi S, Mizogui F. Endothelin-1 decreases the expression of Ephrin-A and B subtypes in cultured rat astrocytes through ETB receptors. Neurosci Lett. 2021, 741, 135393.
Michinaga S, Inoue A, Sonoda K, Mizuguchi H, Koyama Y.* Down-regulation of astrocytic sonic hedgehog by activation of endothelin ETB receptors: Involvement in traumatic brain injury-induced disruption of blood brain barrier in a mouse model. Neurochem Int. 2021, 146:105042.
Michinaga S, Koyama Y* Pathophysiological responses and roles of astrocytes in traumatic brain injury. Int J Mol Sci. 2021. 22, 6418.
Koyama Y.* Endothelin ETB receptor-mediated astrocytic activation: Pathological roles in brain disorders. Int J Mol Sci. 2021, 22, 4333.
Sawahata M, Izumi Y, Akaike A, Kume T*. In vivo brain ischemia-reperfusion model induced by hypoxia-reoxygenation using zebrafish larvae. Brain Res Bull. 2021, 173:45-52.
Matsumoto M, Miyamoto M, Sawahata M, Izumi Y, Takada-Takatori Y, Kume T*. Establishing a high throughput drug screening system for cerebral ischemia using zebrafish larvae. J Pharmacol Sci. 2021, 147:138-142.
2020
Yamaki K*, Terashi M, Ogura S, Inoue S, Naka N, Nakagaki T, Oka N, Koyama Y. Anti-allergic effect of the Src family kinase inhibitor saracatinib. Pharmazie, 2020, 75, 339-343.
Taguchi K, Izumi Y, Takada-Takatori Y, Akaike A, Kume T*. Protective effect of 2',3'-dihydroxy-4',6'-dimethoxychalcone on glutamate-induced neurotoxicity in primary cortical cultures. Biol Pharm Bull. 2020, 43, 184-187.
Inose Y, Izumi Y, Takada-Takatori Y, Akaike A, Koyama Y, Kaneko S, Kume T*. Protective effects of Nrf2-ARE activator on dopaminergic neuronal loss in Parkinson disease model mice: Possible involvement of heme oxygenase-1. Neurosci Lett. 2020, 736, 135268.
Michinaga S, Tanabe A, Nakaya R, Fukutome C, Inoue A, Iwane A, Minato Y, Tujiuchi Y, Miyake D, Mizuguchi H, Koyama Y*. Angiopoietin-1/Tie-2 signal after focal traumatic brain injury is potentiated by BQ788, an ETB receptor antagonist, in the mouse cerebrum: Involvement in recovery of blood-brain barrier function. J Neurochem. 2020, 154:330-348.
Michinaga S, Inoue A, Yamamoto H, Ryu R, Inoue A, Mizuguchi H, Koyama Y*. Endothelin receptor antagonists alleviate blood-brain barrier disruption and cerebral edema in a mouse model of traumatic brain injury: A comparison between bosentan and ambrisentan. Neuropharmacology. 2020, 175, 108182.
2019
Yamamoto K, Izumi Y, Arifuku M, Kume T, Sawada H. α-Synuclein oligomers mediate the aberrant form of spike-induced calcium release from IP3 receptor. Sci Rep. 2019, 9, 15977.
Nakagawa S, Izumi Y, Takada-Takatori Y, Akaike A, Kume T. Increased CCL6 expression in astrocytes and neuronal protection from neuron-astrocyte interactions. Biochem Biophys Res Commun. 2019, 519, 777-782.
Takada-Takatori Y, Takeda Y, Imai R, Izumi Y, Akaike A, Tsuchida K, Kume T. Effects of 2'-3'-dihydroxy-4',6'-dimethoxychalcone derived from green perilla on auricle thickness in chronic contact dermatitis model mice. J Pharmacol Sci. 2019, 141, 17-24.
Takada-Takatori Y, Tomii Y, Takemasa S, Takeda Y, Izumi Y, Akaike A, Tsuchida K, Kume T. Protective Effects of 2',3'-Dihydroxy-4',6'-dimethoxychalcone Derived from Green Perilla Leaves against UV Radiation-Induced Cell Injury in Human Cultured Keratinocytes. Biol Pharm Bull. 2019, 42, 1936-1941.
Iwasaki M, Izuo N, Izumi Y, Takada-Takatori Y, Akaike A, Kume T. Protective Effect of Green Perilla-Derived Chalcone Derivative DDC on Amyloid β Protein-Induced Neurotoxicity in Primary Cortical Neurons. Biol Pharm Bull. 2019, 42, 1942-1946.
Takada-Takatori Y, Nakagawa S, Kimata R, Nao Y, Mizukawa Y, Urushidani T, Izumi Y, Akaike A, Tsuchida K, Kume T. Donepezil modulates amyloid precursor protein endocytosis and reduction by up-regulation of SNX33 expression in primary cortical neurons. Sci Rep. 2019, 9, 11922.
Koyama Y, Sumie S, Nakano Y, Nagao T, Tokumaru S, Michinaga S. Endothelin-1 stimulates expression of cyclin D1 and S-phase kinase-associated protein 2 by activating the transcription factor STAT3 in cultured rat astrocytes. J Biol Chem. 2019, 294, 3920-3933
Michinaga S, Koyama Y. Dual roles of astrocyte-derived factors in regulation of blood-brain barrier function after brain damage. Int J Mol Sci. 2019, 20, pii: E57
2018
Izumi Y, Kataoka H, Inose Y, Akaike A, Koyama Y, Kume T. Neuroprotective effect of an Nrf2-ARE activator identified from a chemical library on dopaminergic neurons. Eur J Pharmacol. 2018, 818, 470-479.
Ikeguchi S, Izumi Y, Kitamura N, Kishino S, Ogawa J, Akaike A, Kume T. Inhibitory effect of the gut microbial linoleic acid metabolites, 10-oxo-trans-11-octadecenoic acid and 10-hydroxy-cis-12-octadecenoic acid, on BV-2 microglial cell activation. J Pharmacol Sci. 2018, 138, 9-15.
Michinaga S, Kimura A, Hatanaka S, Minami S, Asano A, Ikushima Y, Matsui S, Toriyama Y, Fujii M, Koyama Y. Delayed administration of BQ788, an ETB antagonist, after experimental traumatic brain injury promotes recovery of blood-brain barrier function and a reduction of cerebral edema in mice. J Neurotrauma. 2018, 35, 1481-1494.
2016
Toda T, Yoshino S. Enhancement of ovalbumin-speciific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles. Int J Immunopathol Pharmacoll 2016 29, 408-420.
Toda T, Yoshino S. Amorphous nanosilica particles block induction of oral tolerance in mice. J Immunotoxicol 2016 13, 723-728.
Sae-Wong C, Mizutani N, Kangsanant S, Yoshino S. Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice. Eur J Pharmacol 2016 779, 131-137.
Yamaki K, Yoshino S. IgA directly inhibits antigen-dependent B cell activation following distinctive distribution of the antigen in mice. Immunopharmacol Immunotoxicol 2016 38, 131-144.
Yoshino S, Mizutani N. Intranasal exposure to monoclonal antibody Fab fragements to Japanese cedar pollen-induced allergic rhinitis. Br J Pharmacol 2016 173, 1629-1638.
Yamaki K, Yoshino S. A new, rapid in vivo method to evaluate allergic responses through distinctive disribution of a fluoresceent-labeled immune complex: Potential to investigate anti-allergic effects of compounds administered either systemically or topically to the skin. J Immunol Methods 2016 428, 58-68.
2015
Yamaki K, Yoshino S. Establishment of a mouse anti-ovalbumin IgE monoclonal antibody that induces FcεRII (CD23)-dependent activation without FcεRI-dependent acivation. Monoclonal Antib Immunodiagn Immunother 2015 34, 423-431.
Yamaki K, Yoshino S. 3-Chloro-1,2-propanediol (3-MCPD), a carcinogenic food contaminant, inhibits mast cell activation via affecting Ca2+ mobilization. Oyo Yakuri/Pharmacometrics 2015 88, 87-95.
Yamaki K, Yoshino S. The therapeutic potential of monoclonal IgA antibodies in allergic diseases: Suppressive effect of IgA on immune responses induced by re-exposure to antigen in sensitized mice by a monoclonal IgE antibody that binds to a different epitope of the same antigen. Monoclon. Antib. Immunodiagn. Immunother. 2015 34, 83-89.
Mizutani N, Nabe T, Yoshino S. IgE/antigen-mediated enhancement of IgE production is a mechanism underlying the exacerbation of airway inflammation and remodeling in mice. Immunology. 2015 144, 107-115.
Nabe T, Wakamori H, Yano C, Nishiguchi A, Yuasa R, Kido H, Tomiyama Y, Tomoda A, Kida H, Takiguchi A, Matsuda M, Ishihara K, Akiba S, Ohya S, Fukui H, Mizutani N, Yoshino S. Production of interleukin (IL)-33 in the lungs during multiple antigen challenge-induced airway inflammation in mice, and its modulation by a glucocorticoid. Eur. J. Pharmacol. 2015 757, 34-41.
Mizutani N, Nabe T, Yoshino S. Semaphorin 7A plays a critical role in IgE-mediated airway inflammation in mice. Eur. J. Pharmacol. 2015 764, 149-156.
Mizutani N, Sae-Wong C, Kangsanant S, Nabe T, Yoshino S. Thymic stromal lymphopoietin-induced interleukin-17A is involved in the development of IgE-mediated atopic dermatitis-like skin lesions in mice. Immunology. 2015 146, 568-581.
2014
Yoshino S, Maktrirat R, Mizutani N. Suppression of collagen-induced arthritis in mice by anti-collagen antibody Fab fragments. J Arthritis. 2014 3, 2-7.
Matsuoka D, Mizutani N, Sae-Wong C, Yoshino S. Allergen-specific regulation of allergic rhinitis in mice by intranasal exposure to IgG1 monoclonal antibody Fab fragments against pathogenic allergen. Immunol Letter. 2014 161, 149-156.
Mizutani N, Nabe T, Yoshino S. IL-17A promotes the exacerbation of IL-33-induced airway hyperresponsiveness by enhancing neutrophilic inflammation via CXCR2 signaling in mice. J Immunol. 2014 192, 1372-1384.
Yoshino S, Mizutani N, Matsuoka D, Sae-wong C. Intratracheal exposure to Fab fragments of an allergen-specific monoclonal antibody regulates asthmatic responses in mice. Immunology. 2014 141, 617-627.
Yamaki K, Yoshino S. Phosphate ester flame retardant inhibits mast cell activation through blocking store-operated calcium influx. Oyo Yakuri/Pharmacometrics. 2014 87(1/2), 11-20.
Yamaki K, Miyatake K, Nakashima T, Morioka A, Yamamoto M, Ishibashi Y, Ito A, Kuranishi A, Yoshino S. Intravenous IgA complexed with antigen reduces primary antibody response to the antigen and anaphylaxis upon antigen re-exposure by inhibiting Th1 and Th2 activation in mice. Immunopharmacol. Immunotoxicol. 2014 36, 316-328.
Yamaki K, Yoshino S. Remission of food allergy by the Janus kinase inhibitor ruxolitinib in mice. Int. Immunopharmacol. 2014 18, 217-224.
Yamaki K, Nakashima T, Miyatake K, Ishibashi Y, Ito A, Kuranishi A, Taguchi A, Morioka A, Yamamoto M, Yoshino S. IgA attenuates anaphylaxis and subsequent immune responses in mice: possible application of IgA to vaccines. Immunol. Res. 2014 58, 106-117.
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 DD. Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice. Br J Pharmacol. 2013 169, 462-476.
Mizutani N, Nabe T, Yoshino S. Interleukin-33 and alveolar macrophages contribute to the mechanisms underlying the exacerbation of IgE-mediated airway inflammation and remodelling in mice. Immunology. 2013 139, 205-218.
Koobkokkruad T, Kadotani T, Mizutani N, Yoshino S. Efficient induction of arthritis in mice by an arthritogenic 4-clone cocktail of anti-type II collagen monoclonal antibodies recognizing different epitopes of the antigen. Biol Pharm Bull. 2013 36, 1299-1304.
2012
Yamaki K., Yoshino S. Allergy. 2012 67, 114-122. “Tyrosine kinase inhibitor sunitinib relieves systemic and oral antigen-induced anaphylaxes in mice.”
Yamaki K., Yoshino S. Allergy. 2012 67,1259-1270. “Preventive and therapeutic effects of rapamycin, a mammalian target of rapamycin inhibitor, on food allergy in mice.”
Mizutani N., Nabe T., Shimazu M., Yoshino S., Kohno S. Phytother Res. 2012 26, 325-332. “Effect of Ganoderma lucidum on pollen-induced biphasic nasal blockage in a guinea pig model of allergic rhinitis.”
Nabe T., Ikedo A., Hosokawa F., Kishima M., Fujii M., Mizutani N., Yoshino S., Ishihara K., Akiba S., Chaplin DD. Eur J Pharmacol. 2012 677, 154-162. “Regulatory role of antigen-induced interleukin-10, produced by CD4(+) T cells, in airway neutrophilia in a murine model for asthma.”
Mizutani N., Nabe T., Yoshino S. Biol Pharm Bull. 2012 35, 2133-2140. “Exposure to multiwalled carbon nanotubes and allergen promotes early- and late-phase increases in airway resistance in mice.”
Mizutani N., Goshima H., Nabe T., Yoshino S. J Immunol. 2012 188, 5694-5705. “Complement C3a-induced IL-17 plays a critical role in an IgE-mediated late-phase asthmatic response and airway hyperresponsiveness via neutrophilic inflammation in mice.”
2011
Nabe T., Hosokawa F., Matsuya K., Morishita T., Ikedo A., Fujii M., Mizutani N., Yoshino S., Chaplin DD. Life Science. 2011 88, 1127-1135. “Important role of neutrophils in the late asthmatic response in mice.”
Nabe T., Morishita T., Matsuya K., Ikedo A., Fujii M., Mizutani N., Yoshino S. J Pharmacol Sci. 2011 116, 373-383. “Complete dependence on CD4+ cells in late asthmatic response, but limited contribution of the cells to airway remodeling in sensitized mice.”
Yamaki K., Yoshino S. Scand J Immunol. 2011 74, 445-453. “Aspergillus oryzae lectin induces anaphylactoid oedema and mast cell activation through its interaction with fucose of mast cell-bound non-specific IgE.”
Koobkokkruad T., Kadotani T., Hutamekalin P., Mizutani N., Yoshino S. J Inflamm (Lond). 2011 8, 31. “Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity.”
Mizutani N., Goshima H., Nabe T., Yoshino S. Immunol Lett. 2011 141, 235-245. “Establishment and characterization of a murine model for allergic asthma using allergen-specific IgE monoclonal antibody to study pathological roles of IgE.”