Updated on 2024/10/04

Information

 

写真a

 
YAMAMURA KAZUHIKO
 
Organization
Kyushu University Hospital Reserch and Clinical Center for Yusho and Dioxin Assistant Professor
Title
Assistant Professor
External link

Awards

  • Best Presentation Award

    2017.12  

  • 2016年度九州大学医学博士優秀賞

    2017.3   九州大学  

  • 安江賞

    2015.10   第40回 東海皮膚科漢方研究会   ANTI-ALLERGIC MECHANISMS OF JAPANESE HERBAL MEDICINE, YOKUKANSAN ON MAST CELLS

  • 最優秀口演賞

    2014.7   第17回生医研リトリート  

Papers

  • Editorial: Crosstalk: skin cells and immune cells in inflammatory skin diseases

    Yamamura, K; Kim, HJ; Kim, JE

    FRONTIERS IN IMMUNOLOGY   15   1472313   2024.8   ISSN:1664-3224

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    DOI: 10.3389/fimmu.2024.1472313

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  • Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood

    Czarnowicki, T; David, E; Yamamura, K; Han, J; He, H; Pavel, AB; Glickman, J; Erickson, T; Estrada, Y; Krueger, JG; Rangel, SM; Paller, AS; Guttman-Yassky, E

    ALLERGY   2024.7   ISSN:0105-4538 eISSN:1398-9995

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    Background: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined. Objective: To compare the frequency of B-cell subsets in blood of 0–5, 6–11, 12–17, and ≥18 years old patients with AD versus age-matched controls. Methods: Flow cytometry was used to measure B-cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate-to-severe AD and age-matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometry panel were used to determine frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgEs) levels were measured using ImmunoCAP®. Results: Adolescents with AD had lower frequencies of major B-cells subsets (p <.03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p <.04). In AD patients, multiple positive correlations were observed between IL-17-producing T-cells and B-cell subsets, most significantly non-switched memory (NSM) B-cells (r =.41, p =.0005). AD severity positively correlated with a list of B-cell subsets (p <.05). IL-9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls. Conclusions: Multiple correlations between B-cells and T-cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B-cell signature during adolescence, with concurrent allergen sensitization and IL-9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march.

    DOI: 10.1111/all.16225

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  • Difamilast, a Topical Phosphodiesterase 4 Inhibitor, Produces Soluble ST2 via the AHR-NRF2 Axis in Human Keratinocytes

    Tsuji, G; Yumine, A; Kawamura, K; Takemura, M; Kido-Nakahara, M; Yamamura, K; Nakahara, T

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   25 ( 14 )   2024.7   ISSN:1661-6596 eISSN:1422-0067

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    Difamilast, a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be effective in the treatment of atopic dermatitis (AD), although the mechanism involved remains unclear. Since IL-33 plays an important role in the pathogenesis of AD, we investigated the effect of difamilast on IL-33 activity. Since an in vitro model of cultured normal human epidermal keratinocytes (NHEKs) has been utilized to evaluate the pharmacological potential of adjunctive treatment of AD, we treated NHEKs with difamilast and analyzed the expression of the suppression of tumorigenicity 2 protein (ST2), an IL-33 receptor with transmembrane (ST2L) and soluble (sST2) isoforms. Difamilast treatment increased mRNA and protein levels of sST2, a decoy receptor suppressing IL-33 signal transduction, without affecting ST2L expression. Furthermore, supernatants from difamilast-treated NHEKs inhibited IL-33-induced upregulation of TNF-α, IL-5, and IL-13 in KU812 cells, a basophil cell line sensitive to IL-33. We also found that difamilast activated the aryl hydrocarbon receptor (AHR)–nuclear factor erythroid 2-related factor 2 (NRF2) axis. Additionally, the knockdown of AHR or NRF2 abolished the difamilast-induced sST2 production. These results indicate that difamilast treatment produces sST2 via the AHR–NRF2 axis, contributing to improving AD symptoms by inhibiting IL-33 activity.

    DOI: 10.3390/ijms25147910

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  • A Case of Intractable Lower Leg Ulcer with Idiopathic Multicentric Castleman's Disease

    SUGI Yuta, YAMAMURA Kazuhiko, TAKEI Itsuki, NAKAHARA Makiko, ICHIKI Toshio, MIYAWAKI Kota, YAMAMOTO Hidetaka, YAMAMURA Mika, NAKAHARA Takeshi

    The Nishinihon Journal of Dermatology   86 ( 3 )   233 - 237   2024.6   ISSN:03869784 eISSN:18804047

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    Language:Japanese   Publisher:Western Division of Japanese Dermatological Association  

    DOI: 10.2336/nishinihonhifu.86.233

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  • Gram‐negative anaerobes elicit a robust keratinocytes immune response with potential insights into <scp>HS</scp> pathogenesis

    Samuel C. Williams, Sandra Garcet, Hong Hur, Shunsuke Miura, Juana Gonzalez, Kristina Navrazhina, Mika Yamamura‐Murai, Kazuhiko Yamamura, Xuan Li, John Frew, Vincent A. Fischetti, Uri Sela, James G. Krueger

    Experimental Dermatology   33 ( 5 )   2024.4   ISSN:0906-6705 eISSN:1600-0625

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Abstract

    Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram‐positive facultative (GPs) Staphylococcus species and gram‐negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat‐killed and co‐incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT‐qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co‐staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL‐17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan‐JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS‐relevant genes, including many genes in the IL‐17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

    DOI: 10.1111/exd.15087

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  • The therapeutic AHR-modulating agent Tapinarof regulates semaphorin 3A expression in human keratinocytes via NRF2. International journal

    Gaku Tsuji, Ayako Yumine, Kazuhiko Yamamura, Masaki Takemura, Makiko Kido-Nakahara, Takamichi Ito, Takeshi Nakahara

    The Journal of investigative dermatology   144 ( 3 )   710 - 713.e8   2024.3   ISSN:0022-202X eISSN:1523-1747

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    DOI: 10.1016/j.jid.2023.10.002

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  • Regulatory Mechanism of the IL-33-IL-37 Axis via Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. International journal

    Gaku Tsuji, Kazuhiko Yamamura, Koji Kawamura, Makiko Kido-Nakahara, Takamichi Ito, Takeshi Nakahara

    International journal of molecular sciences   24 ( 19 )   2023.10   ISSN:1661-6596 eISSN:1422-0067

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    Interleukin (IL)-33 and IL-37 have been identified as novel cytokines involved in various inflammatory diseases. However, their specific roles remain largely unknown. Recent studies have shown that IL-33, which triggers inflammation, and IL-37, which suppresses it, cooperatively regulate the balance between inflammation and anti-inflammation. IL-33 and IL-37 are also deeply involved in the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Furthermore, a signaling pathway by which aryl hydrocarbon receptor (AHR), a receptor for dioxins, regulates the expression of IL-33 and IL-37 has been revealed. Here, we outline recent findings on the mechanisms regulating IL-33 and IL-37 expression in AD and psoriasis. IL-33 expression is partially dependent on mitogen-activated protein kinase (MAPK) activation, and IL-37 has a role in suppressing MAPK in human keratinocytes. Furthermore, IL-33 downregulates skin barrier function proteins including filaggrin and loricrin, thereby downregulating the expression of IL-37, which colocalizes with these proteins. This leads to an imbalance of the IL-33-IL-37 axis, involving increased IL-33 and decreased IL-37, which may be associated with the pathogenesis of AD and psoriasis. Therefore, AHR-mediated regulation of the IL-33-IL-37 axis may lead to new therapeutic strategies for the treatment of AD and psoriasis.

    DOI: 10.3390/ijms241914633

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  • Staphylococcus Aureus and Streptococcus Pyogenes Induce Psoriasis-Related Transcriptomes Augmented by IL-17A and TNF-α. International journal

    Shunsuke Miura, Yohei Ichimura, Uri Sela, Sandra Garcet, Charissa Salud-Gnilo, Xuan Li, Juana Gonzalez, Mika Murai-Yamamura, Kazuhiko Yamamura, Darshna Rambhia, Norma Kunjravia, James G Krueger

    The Journal of investigative dermatology   143 ( 8 )   1613 - 1617   2023.8   ISSN:0022202X

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    DOI: 10.1016/j.jid.2022.12.026

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  • Cathelicidin Antimicrobial Peptide LL37 Induces Toll-Like Receptor 8 and Amplifies IL-36γ and IL-17C in Human Keratinocytes. International journal

    Shunsuke Miura, Sandra Garcet, Xuan Li, Inna Cueto, Charissa Salud-Gnilo, Norma Kunjravia, Kazuhiko Yamamura, Juana Gonzalez, Mika Murai-Yamamura, Darshna Rambhia, James G Krueger

    The Journal of investigative dermatology   143 ( 5 )   832 - 841   2023.5   ISSN:0022202X

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    LL37 is produced by skin injury and bacterial infection and plays an important role in the early stages of psoriasis. In particular, the intracellular receptors toll-like receptors (TLR)3, TLR7, TLR8, and TLR9 are thought to be involved in the pathogenesis of psoriasis in conjunction with LL37, but the interaction between TLR7/8 and LL37 in keratinocytes (KCs) remains unclear. This study aimed to clarify the relationship between LL37 and TLR7/8 in KCs and their involvement in the pathogenetic pathways seen in psoriasis using cultured KCs and skin samples of patients with psoriasis. TLR7/8 was induced by LL37 in KCs. TLR8 but not TLR7 functionally induced many psoriasis-related molecules, whereas IL-17C was not altered by the blockade of TLR7/8. Although costimulation of LL37 with self-RNA/DNA did not show any interaction, LL37 itself would promote psoriasis-related genes. IL-36 receptor antagonistic antibody suppressed IL-17C induced by LL37. In psoriatic epidermis, LL37, TLRs, IL-17C, and IL-36γ expressions were increased and coexpressed with each other. Thus, we concluded that LL37 activates TLR8 in KCs and induces IL-17C through the induction of IL-36γ. Regulation of TLR8 or LL37 in KCs could be a potential therapeutic strategy for psoriatic inflammation.

    DOI: 10.1016/j.jid.2022.10.017

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  • PDE4 inhibition by difamilast regulates filaggrin and loricrin expression via keratinocyte proline-rich protein in human keratinocytes. International journal

    Gaku Tsuji, Akiko Hashimoto-Hachiya, Ayako Yumine, Masaki Takemura, Makiko Kido-Nakahara, Takamichi Ito, Kazuhiko Yamamura, Takeshi Nakahara

    Journal of dermatological science   110 ( 2 )   61 - 68   2023.5   ISSN:0923-1811 eISSN:1873-569X

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    BACKGROUND: Difamilast, a topical phosphodiesterase 4 (PDE4) inhibitor, has been shown to be effective for treating atopic dermatitis (AD), but the molecular mechanism involved is unclear. Since skin barrier dysfunction including reduced expression of filaggrin (FLG) and loricrin (LOR) contributes to AD development, difamilast treatment may be able to improve this dysfunction. PDE4 inhibition increases transcriptional activity of cAMP-responsive element binding protein (CREB). Therefore, we hypothesized that difamilast may affect FLG and LOR expression via CREB in human keratinocytes. OBJECTIVE: To elucidate the mechanism by which difamilast regulates FLG and LOR expression via CREB in human keratinocytes. METHODS: We analyzed normal human epidermal keratinocytes (NHEKs) treated with difamilast. RESULTS: We observed increases of intracellular cAMP levels and CREB phosphorylation in difamilast (5 μM)-treated NHEKs. Next, we found that difamilast treatment increased mRNA and protein levels of FLG and LOR in NHEKs. Since reduced expression of keratinocyte proline-rich protein (KPRP) is reported to be involved in skin barrier dysfunction in AD, we examined KPRP expression in difamilast-treated NHEKs. We found that difamilast treatment increased mRNA and protein levels of KPRP in NHEKs. Furthermore, KPRP knockdown using siRNA transfection abolished the upregulation of FLG and LOR in difamilast-treated NHEKs. Finally, CREB knockdown canceled the upregulation of FLG, LOR, and KPRP in difamilast-treated NHEKs, indicating that PDE4 inhibition by difamilast treatment positively regulates FLG and LOR expression via the CREB-KPRP axis in NHEKs. CONCLUSION: These findings may provide further guidance for therapeutic strategies in the treatment of AD using difamilast.

    DOI: 10.1016/j.jdermsci.2023.04.007

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  • The role of OX40/OX40L axis in atopic dermatitis

    Yamamura, K; Yamamura, M; Garcet, S; Dahabreh, D; Gonzalez, J; Miura, S; Williams, S; Nakahara, T; Krueger, J; Guttman-Yassky, E

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   143 ( 5 )   S11 - S11   2023.5   ISSN:0022-202X eISSN:1523-1747

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  • Tapinarof, a therapeutic AHR-modulating agent, induces semaphorin 3A production via NRF2 in human keratinocytes: Implications for atopic dermatitis

    Tsuji, G; Takai-Yumine, A; Takemura, M; Yamamura, K; Ito, T; Kido-Nakahara, M; Nakahara, T

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   143 ( 5 )   S189 - S189   2023.5   ISSN:0022-202X eISSN:1523-1747

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  • PDE4 inhibition by difamilast regulates filaggrin and loricrin expression via keratinocyte proline-rich protein in human keratinocytes(タイトル和訳中)

    Tsuji Gaku, Hashimoto-Hachiya Akiko, Yumine Ayako, Takemura Masaki, Kido-Nakahara Makiko, Ito Takamichi, Yamamura Kazuhiko, Nakahara Takeshi

    Journal of Dermatological Science   110 ( 2 )   61 - 68   2023.5   ISSN:0923-1811

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  • Novel Therapeutic Targets for the Treatment of Atopic Dermatitis. International journal

    Gaku Tsuji, Kazuhiko Yamamura, Koji Kawamura, Makiko Kido-Nakahara, Takamichi Ito, Takeshi Nakahara

    Biomedicines   11 ( 5 )   2023.4   ISSN:2227-9059 eISSN:2227-9059

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    Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to the recognition of multiple novel therapeutic targets. For systemic therapy, new biologic agents that target IL-13, IL-22, IL-33, the IL-23/IL-17 axis, and OX40-OX40L are being developed. Binding of type II cytokines to their receptors activates Janus kinase (JAK) and its downstream signal, namely signal transduction and activator of transcription (STAT). JAK inhibitors block the activation of the JAK-STAT pathway, thereby blocking the signaling pathways mediated by type II cytokines. In addition to oral JAK inhibitors, histamine H4 receptor antagonists are under investigation as small-molecule compounds. For topical therapy, JAK inhibitors, aryl hydrocarbon receptor modulators, and phosphodiesterase-4 inhibitors are being approved. Microbiome modulation is also being examined for the treatment of AD. This review outlines current and future directions for novel therapies of AD that are currently being investigated in clinical trials, focusing on their mechanisms of action and efficacy. This supports the accumulation of data on advanced treatments for AD in the new era of precision medicine.

    DOI: 10.3390/biomedicines11051303

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  • Identification of a functional DOCK8 gene polymorphism associated with atopic dermatitis. International journal

    Kazufumi Kunimura, Kazuhiko Yamamura, Takeshi Nakahara, Makiko Kido-Nakahara, Takehito Uruno, Yoshinori Fukui

    Allergy   77 ( 12 )   3670 - 3672   2022.12   ISSN:0105-4538 eISSN:1398-9995

  • The Dawn of a New Era in Atopic Dermatitis Treatment. International journal

    Kazuhiko Yamamura, Takeshi Nakahara

    Journal of clinical medicine   11 ( 20 )   2022.10   ISSN:2077-0383 eISSN:2077-0383

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    Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, and the condition is typified by barrier dysfunction and immune dysregulation. Recent studies have characterized various phenotypes and endotypes of AD and elucidated the mechanism. Numerous topical and systemic narrow targeting therapies for AD have been developed according to these findings. Topical medications, including Janus kinase (JAK) inhibitors, phosphodiesterase 4 inhibitors, and the aryl hydrocarbon receptor agonist tapinarof, are effective and safe for AD compared to topical corticosteroids. Oral JAK inhibitors and monoclonal antibodies targeting interleukin (IL)-4, IL-13, IL-31, IL-33, OX40, thymic stromal lymphopoietin, and sphingosine 1-phosphate signaling have displayed outstanding efficacy against moderate-to-severe AD. We are currently in a new era of AD treatment.

    DOI: 10.3390/jcm11206145

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  • Concordance in judgment of clinical borders of basal cell carcinomas in Japanese patients: A preliminary study of JCOG2005 (J-BASE-MARGIN)

    Kamimura, A; Nakamura, Y; Takenouchi, T; Matsushita, S; Omodaka, T; Yamamura, K; Uchi, H; Yoshikawa, S; Yanagisawa, H; Ito, T; Kiyohara, Y; Nakamura, Y; Aoki, M; Ishizuki, S; Oashi, K; Miyagawa, T; Maeda, T; Ogata, D; Hatta, N; Ohe, S; Isei, T; Takahashi, A; Umeda, Y; Yamaguchi, B; Ishikawa, M; Horimoto, K; Fujsawa, Y; Uehara, J; Shibayama, Y; Kiniwa, Y; Kawahara, Y; Matsuya, T; Uhara, H; Kato, J; Nakamura, Y; Murakami, T; Namikawa, K; Yoshino, K; Funakoshi, T; Takatsuka, S; Matsui, Y; Sasaki, J; Koga, H; Yokota, K; Komori, T; Fukushima, S; Yamazaki, N

    JOURNAL OF DERMATOLOGY   49 ( 9 )   837 - 844   2022.9   ISSN:0385-2407 eISSN:1346-8138

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  • Confirmatory trial of narrower side margin excision for head and neck basal cell carcinoma in the Japanese (East Asian) population: JCOG2005 (J-BASE-MARGIN).

    Nakamura, Y; Sano, Y; Kataoka, T; Shibata, T; Fukuda, H; Matsushita, S; Fujisawa, Y; Takenouchi, T; Omodaka, T; Yamamura, K; Aoki, M; Uchi, H; Tsutsui, K; Yoshikawa, S; Ogata, D; Yanagisawa, H; Omatsu, J; Ito, T; Namikawa, K; Yamazaki, N

    JOURNAL OF CLINICAL ONCOLOGY   40 ( 16 )   2022.6   ISSN:0732-183X eISSN:1527-7755

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  • TH 2 cytokines and Staphylococcus aureus cooperatively induce atopic dermatitis-like transcriptomes. International journal

    Mika Murai-Yamamura, Sandra Garcet, Kazuhiko Yamamura, Juana Gonzalez, Shunsuke Miura, Xuan Li, Hong Hur, Emma Guttman-Yassky, James G Krueger

    Allergy   76 ( 11 )   3534 - 3537   2021.11

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    DOI: 10.1111/all.15035

  • IL-36 and IL-17A Cooperatively Induce a Psoriasis-Like Gene Expression Response in Human Keratinocytes. International journal

    141 ( 8 )   2086 - 2090   2021.8

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    DOI: 10.1016/j.jid.2021.01.019

  • OVOL2-Mediated ZEB1 Downregulation May Prevent Promotion of Actinic Keratosis to Cutaneous Squamous Cell Carcinoma. International journal

    Maho Murata, Takamichi Ito, Yuka Tanaka, Kazuhiko Yamamura, Kazuhisa Furue, Masutaka Furue

    Journal of clinical medicine   9 ( 3 )   2020.2

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    DOI: 10.3390/jcm9030618

  • Selective role of neurokinin B in IL-31-induced itch response in mice. International journal

    Daiji Sakata, Takehito Uruno, Keisuke Matsubara, Tsugunobu Andoh, Kazuhiko Yamamura, Yuki Magoshi, Kazufumi Kunimura, Yasuhisa Kamikaseda, Masutaka Furue, Yoshinori Fukui

    The Journal of allergy and clinical immunology   144 ( 4 )   1130 - 1133   2019.10

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    DOI: 10.1016/j.jaci.2019.06.031

  • Serum squamous cell carcinoma antigen (SCCA)-2 correlates with clinical severity of pediatric atopic dermatitis in Ishigaki cohort. International journal

    Satoshi Takeuchi, Norihiro Furusyo, Junya Ono, Yoshinori Azuma, Masaki Takemura, Hitokazu Esaki, Kazuhiko Yamamura, Yasutaka Mitamura, Gaku Tsuji, Mari Kiyomatsu-Oda, Jun Hayashi, Kenji Izuhara, Masutaka Furue

    Journal of dermatological science   95 ( 2 )   70 - 75   2019.8

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    DOI: 10.1016/j.jdermsci.2019.07.005

  • Cyto/chemokine profile of in vitro scratched keratinocyte model: Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon. International journal

    Kazuhisa Furue, Takamichi Ito, Yuka Tanaka, Ayako Yumine, Akiko Hashimoto-Hachiya, Masaki Takemura, Maho Murata, Kazuhiko Yamamura, Gaku Tsuji, Masutaka Furue

    Journal of dermatological science   94 ( 1 )   244 - 251   2019.4

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    DOI: 10.1016/j.jdermsci.2019.04.002

  • Tryptophan photo-product FICZ upregulates AHR/MEK/ERK-mediated MMP1 expression: Implications in anti-fibrotic phototherapy. International journal

    Mika Murai, Kazuhiko Yamamura, Akiko Hashimoto-Hachiya, Gaku Tsuji, Masutaka Furue, Chikage Mitoma

    Journal of dermatological science   91 ( 1 )   97 - 103   2018.7

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    DOI: 10.1016/j.jdermsci.2018.04.010

  • Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye. International journal

    Tetsuya Sakurai, Takehito Uruno, Yuki Sugiura, Takaaki Tatsuguchi, Kazuhiko Yamamura, Miho Ushijima, Yuko Hattori, Mutsuko Kukimoto-Niino, Chiemi Mishima-Tsumagari, Mayuki Watanabe, Makoto Suematsu, Yoshinori Fukui

    Science signaling   11 ( 541 )   2018.7

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    DOI: 10.1126/scisignal.aao4874

  • Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis. International journal

    Kazuhisa Furue, Kazuhiko Yamamura, Gaku Tsuji, Chikage Mitoma, Hiroshi Uchi, Takeshi Nakahara, Makiko Kido-Nakahara, Takafumi Kadono, Masutaka Furue

    Acta dermato-venereologica   98 ( 1 )   5 - 13   2018.1

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    DOI: 10.2340/00015555-2808

  • The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction. International journal

    Kazuhiko Yamamura, Takehito Uruno, Akira Shiraishi, Yoshihiko Tanaka, Miho Ushijima, Takeshi Nakahara, Mayuki Watanabe, Makiko Kido-Nakahara, Ikuya Tsuge, Masutaka Furue, Yoshinori Fukui

    Nature communications   8   13946 - 13946   2017.1

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    DOI: 10.1038/ncomms13946

  • Levels of immunoglobulin E specific to the major food allergen and chemokine (C-C motif) ligand (CCL)17/thymus and activation regulated chemokine and CCL22/macrophage-derived chemokine in infantile atopic dermatitis on Ishigaki Island. International journal

    Hitokazu Esaki, Satoshi Takeuchi, Norihiro Furusyo, Kazuhiko Yamamura, Sayaka Hayashida, Gaku Tsuji, Masaki Takemura, Jun Hayashi, Masutaka Furue

    The Journal of dermatology   43 ( 11 )   1278 - 1282   2016.11

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    DOI: 10.1111/1346-8138.13360

  • Incidence, serum IgE and TARC/CCL17 levels in atopic dermatitis associated with other allergic diseases: an update from the Ishigaki cohort. International journal

    Satoshi Takeuchi, Hitokazu Esaki, Norihiro Furusyo, Sayaka Hayashida, Kazuhiko Yamamura, Gaku Tsuji, Masaki Takemura, Jun Hayashi, Masutaka Furue

    Acta dermato-venereologica   95 ( 4 )   480 - 4   2015.4

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    DOI: 10.2340/00015555-1989

  • Anti-allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells. International journal

    Kazuhiko Yamamura, Shiori Kato, Takahiro A Kato, Yoshito Mizoguchi, Akira Monji, Shigenobu Kanba, Masutaka Furue, Satoshi Takeuchi

    The Journal of dermatology   41 ( 9 )   808 - 14   2014.9

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    DOI: 10.1111/1346-8138.12578

  • DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation. International journal

    Kana Ogawa, Yoshihiko Tanaka, Takehito Uruno, Xuefeng Duan, Yosuke Harada, Fumiyuki Sanematsu, Kazuhiko Yamamura, Masao Terasawa, Akihiko Nishikimi, Jean-François Côté, Yoshinori Fukui

    211 ( 7 )   1407 - 19   2014.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    Mast cells play a key role in the induction of anaphylaxis, a life-threatening IgE-dependent allergic reaction, by secreting chemical mediators that are stored in secretory granules. Degranulation of mast cells is triggered by aggregation of the high-affinity IgE receptor, FcεRI, and involves dynamic rearrangement of microtubules. Although much is known about proximal signals downstream of FcεRI, the distal signaling events controlling microtubule dynamics remain elusive. Here we report that DOCK5, an atypical guanine nucleotide exchange factor (GEF) for Rac, is essential for mast cell degranulation. As such, we found that DOCK5-deficient mice exhibit resistance to systemic and cutaneous anaphylaxis. The Rac GEF activity of DOCK5 is surprisingly not required for mast cell degranulation. Instead, DOCK5 associated with Nck2 and Akt to regulate microtubule dynamics through phosphorylation and inactivation of GSK3β. When DOCK5-Nck2-Akt interactions were disrupted, microtubule formation and degranulation response were severely impaired. Our results thus identify DOCK5 as a key signaling adaptor that orchestrates remodeling of the microtubule network essential for mast cell degranulation.

    DOI: 10.1084/jem.20131926

  • Decrease of reactive oxygen species and reciprocal increase of nitric oxide in human dermal endothelial cells by Bidens pilosa extract: a possible explanation of its beneficial effect on livedo vasculopathy. International journal

    Futoshi Kohda, Masakazu Takahara, Akiko Hachiya, Kenjiro Takei, Gaku Tsuji, Kazuhiko Yamamura, Masutaka Furue

    Journal of dermatological science   72 ( 1 )   75 - 7   2013.10

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    Language:English  

    DOI: 10.1016/j.jdermsci.2013.05.008

  • Subcutaneous calcification of the lower legs in a patient with mixed connective tissue disease. International journal

    Kazuhiko Yamamura, Masakazu Takahara, Kana Masunaga, Takuya Sawabe, Masaki Kitano, Toshihiko Mashino, Masutaka Furue

    The Journal of dermatology   38 ( 8 )   791 - 3   2011.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1346-8138.2010.01177.x

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Presentations

Research Projects

  • アトピー性皮膚炎における新規そう痒惹起物質の同定とその感知機構の解明

    Grant number:23K15285  2023 - 2025

    科学研究費助成事業  若手研究(A)

    山村 和彦

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    Authorship:Principal investigator  Grant type:Scientific research funding

    本研究では、ヒト感覚神経細胞をこれまで報告のあったアトピー性皮膚炎患者血球細胞で発現が変化しているサイトカイン/生理活性脂質で刺激し、解析することで、アトピー性皮膚炎痒みに関わりのある新規そう痒惹起物質の同定、及びその産生制御機構とシグナル伝達経路の解明、新たな創薬標的の導出を目的とする。

    CiNii Research

  • iPS細胞由来ヒト感覚神経を用いたアトピー性皮膚炎における痒みのメカニズムの探求

    Grant number:22K20686  2022 - 2023

    日本学術振興会  科学研究費助成事業  研究活動スタート支援

    山村 和彦

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    Authorship:Principal investigator  Grant type:Scientific research funding

    アトピー性皮膚炎は国民の7-15%が罹患し、多くの患者さんが激しい痒みに悩まされています。これまでヒトの痒みに関連する研究は、ヒト末梢神経が入手困難だったこともあり、ほとんどなされてきませんでした。本研究は、近年開発されたヒトiPS細胞由来の末梢感覚神経を用いることで、アトピー性皮膚炎に特徴的な痒みを引き起こすメカニズムとそれに重要な物質を特定することを目的にしています。

    CiNii Research

  • 炎症性皮膚疾患のThサブセット偏移を制御する生理活性脂質の同定と疾患モデルの創出

    2020 - 2022

    日本学術振興会  海外特別研究員

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    Authorship:Principal investigator  Grant type:Joint research

  • アトピー性皮膚炎における新しい共刺激分子の特徴と役割

    2018 - 2019

    アステラス病態代謝研究会

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    Authorship:Principal investigator  Grant type:Contract research

Travel Abroad

  • 2018.11 - 2022.3

    Staying countory name 1:United States   Staying institution name 1:The Rockefeller University (USA), Laboratory for Investigative Dermatology