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• Oral allergy induction through skin exposure to previously tolerated food antigens in murine models

  Yamashita Hirotaka, Matsuhara Hiroki, Tanaka Hiroyuki, Inagaki Naoki, Tsutsui Masato

  Journal of Pharmacological Sciences   152   76 - 85   2023.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Prophylactic steroid use is ineffective in food allergy: A randomized-controlled clinical trial and a murine model.

  Matsui T, Yamashita H, Kitamura K, Makino A, Takasato Y, Sugiura S, Ito K

  Allergy ( Allergy: European Journal of Allergy and Clinical Immunology )    2022.07 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Spontaneous pulmonary emphysema in mice lacking all three nitric oxide synthase isoforms.

  Kato K, Tsutsui M, Noguchi S, Iha Y, Naito K, Ogoshi T, Nishida C, Tahara M, Yamashita H, Wang KY, Toyohira Y, Yanagihara N, Masuzaki H, Shimokawa H, Tanimoto A, Yatera K

  Scientific reports ( Scientific Reports )  11 ( 1 ) 22088 - 22088   2021.11 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  The roles of endogenous nitric oxide (NO) derived from the entire NO synthases (NOSs) system have yet to be fully elucidated. We addressed this issue in mice in which all three NOS isoforms were deleted. Under basal conditions, the triple n/i/eNOSs-/- mice displayed significantly longer mean alveolar linear intercept length, increased alveolar destructive index, reduced lung elastic fiber content, lower lung field computed tomographic value, and greater end-expiratory lung volume as compared with wild-type (WT) mice. None of single NOS-/- or double NOSs-/- genotypes showed such features. These findings were observed in the triple n/i/eNOSs-/- mice as early as 4 weeks after birth. Cyclopaedic and quantitative comparisons of mRNA expression levels between the lungs of WT and triple n/i/eNOSs-/- mice by cap analysis of gene expression (CAGE) revealed that mRNA expression levels of three Wnt ligands and ten Wnt/β-catenin signaling components were significantly reduced in the lungs of triple n/i/eNOSs-/- mice. These results provide the first direct evidence that complete disruption of all three NOS genes results in spontaneous pulmonary emphysema in juvenile mice in vivo possibly through down-regulation of the Wnt/β-catenin signaling pathway, demonstrating a novel preventive role of the endogenous NO/NOS system in the occurrence of pulmonary emphysema.

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• Impact of orally-administered oligosaccharides in a murine model of food allergy: Impact of oligosaccharides on food allergy

  Yamashita H.

  Journal of Functional Foods ( Journal of Functional Foods )  85   2021.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Food allergy is a refractory condition for which there are no standard effective therapies. Prebiotic supplementation such as oligosaccharides in infants was found to be associated with decreased risk of allergic diseases. Raffinose and stachyose are the major oligosaccharides identified in beans; these oligosaccharides have properties of regulating homeostasis. In this study, we explored the use of oligosaccharides as a means to prevent food allergy using an ovalbumin (OVA) sensitization and challenge model in which reductions in body temperature and diarrhea were evaluated. Raffinose and stachyose were administered ad libitum in drinking water for five weeks from one week prior the first sensitization through the final oral administration of OVA. Among our findings, treatment with stachyose suppressed allergic diarrhea and prevented elevations in OVA-specific immunoglobulin (Ig)G1. We hypothesize that suppression of these responses was associated with the actions of regulatory T cells and promoted by utilization of the oligosaccharides by intestinal microbiota. Taken together, our findings suggest that daily ingestion of oligosaccharides might be effective for the prevention of food allergy.

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• Staphylococcal Phage in Combination with Staphylococcus Epidermidis as a Potential Treatment for Staphylococcus Aureus-Associated Atopic Dermatitis and Suppressor of Phage-Resistant Mutants.

  Shimamori Y, Mitsunaka S, Yamashita H, Suzuki T, Kitao T, Kubori T, Nagai H, Takeda S, Ando H

  Viruses ( Viruses )  13 ( 1 )   2020.12 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.

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• 魚アレルギー免疫療法剤の開発を目的としたスクリーニングモデルの確立

  岩井 恵美, 大日方 翔太朗, 下條 尚志, 中村 政志, 山下 弘高, 稲垣 直樹, 矢上 晶子, 松永 佳世子, 田中 宏幸

  アレルギー ( (一社)日本アレルギー学会 )  67 ( 4-5 ) 559 - 559   2018.05

   

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2021.04  -  2024.03 

  Direct: 3,200,000 (YEN)  Overheads: 4,160,000 (YEN)  Total: 960,000 (YEN)

• "Allergy via Intestine" and "Allergy via Skin"

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2019.04  -  2023.03 

  Direct: 3,400,000 (YEN)  Overheads: 4,420,000 (YEN)  Total: 1,020,000 (YEN)

• Structural and functional analyses of bioactive oligosaccharides in kidney beans.

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2016.04  -  2020.03 

  Investigator(s): Kimura Mariko 

  Direct: 0 (YEN)  Overheads: 0 (YEN)  Total: 0 (YEN)

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  In this study, we found for the first time that free plant complex sugar chains (Man3Xyl1Fuc1GlcNAc2, M3FX) were contained in a large amount of several ten mg% of the weight of white kidney bean (Tebo), and established the preparation method. We have already demonstrated that M3FX suppresses IL-4 production from T cells (Th2). Therefore, Tebo is a good source of M3FX which is thought to have immunoregulatory activity. In addition, the anti-allergic effect of stachyose, which is a major constituent sugar of many kinds of beans, was confirmed using OVA-induced food allergic mice (blood protease p-1 inhibition, p<0.01). These results demonstrated that kidney beans contain several biofunctional oligosaccharides with immunomodulatory activity.