2011 Fiscal Year Final Research Report
Challenge to the developmental study of new biomarker and new treatment in recalcitrant allergic skin disease
| Project/Area Number |
21591471
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | International University of Health and Welfare (2011)
Yokohama City University (2009-2010) |
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Principal Investigator |
IKEZAWA Zenro 国際医療福祉大学, 熱海病院皮膚科 (90046128)
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| Project Period (FY) |
2009 – 2011
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| Keywords | アトピー性皮膚炎 / ドライスキン / 痒み / 皮表の黄色ブドウ球菌叢 / IL-18 / NGF / Semaphorin 3A(Sema3A) / アレルギー性鼻炎 / コラーゲントリペプチド(CTP) |
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| Research Abstract |
1) IL-18 levels in the horny layer were significantly higher in the skin lesions of patients with AD than in healthy controls and correlated with SCORAD, levels of serum IL-18, IgE, lactate dehydrogenase(LDH), thymus and activation-regulated chemokine(TARC), blood eosinophils and transepidermal water loss(TEWL). In the AD group with serum IgE<1500 IU mL, significantly higher IL-18 levels were observed in the horny layer of patients colonized with S. aureus compared with those who were not. From these results, it may be concluded that epidermal IL-18 production is associated with the severity of AD, that staphylococcus aureus colonization seems to contribute to this IL-18 production, especially in the AD group with relatively low IgE production, and that tape stripping provides an easy and noninvasive method to assess epidermal IL-18 production by ELISA. 2-1) Pruritus is a common symptom of psoriasis, which affects quality of life. This symptom accompanies the hyperinnervation of sensor
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y C-fibres in psoriatic lesions. Two extracellular molecules, nerve growth factor(NGF) and semaphorin-3A, regulate C-fibre extension. In this study, the expression levels of these 2 molecules in biopsy specimens from psoriatic and healthy skin were quantified by immune-histochemistry and quantitative reverse-transcription PCR. Semaphorin-3A expression was lower in the psoriatic samples compared with the healthy samples, whereas NGF was higher. C-fibre innervation in the epidermis was also increased in psoriatic skin. Semaphorin-3A mRNA expression was negatively correlated with itch intensity and severity of psoriasis. We propose that decreased semaphorin-3A and increased NGF expression levels may trigger the outgrowth of C-fibres, leading to pruritus. 2-2) Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis(AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A(Sema3A) has been previously shown to restrict innervation of sensory neurons, it is presumed that reduced Sema3A expression in the nasal mucosa might contribute to the hypersensitivity. Analysis of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression of Sema3A in the nasal epithelium, which was accompanied by an increased nerve fiber density in the lamina propria of the turbinate. In rescue experiments, intranasal administration of recombinant Sema3A in the AR model mice alleviated sneezing and nasal rubbing symptoms. In addition, histological examinations also revealed that nerve fiber density was decreased in the lamina propria of the Sema3A-treated nasal turbinate. These results suggest that the nasal hypersensitivity of AR may be attributed to reduction of Sema3A expression and intranasal administration of Sema3A may provide a novel approach to alleviate the allergic symptoms for AR treatment. 3) CTP enhanced hyaluronic acid production in human dermal fibroblasts in vitro and in murine skin in vivo. Oral administration of CTP in acetone-induced dry skin model mice significantly decreased TEWL and suppressed scratching behavior. Intraepidermal nerve growth was dramatically inhibited in CTP-treated mice. Quantitative PCR analysis and immunohistochemical study revealed that CTP abolished the increased NGF and decreased Sema3A levels induced by acetone treatment. From these results, it may be concluded that oral administration of CTP improves dry skin and normalizes axon-guidance factors in the epidermis in addition to reducing pruritus. CTP may be used in a new therapeutic strategy against dry skin and pruritus. Less
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Research Products
(46 results)
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[Journal Article] Decreased Expression of Semaphorin-3A, a Neurite-Collapsing Factor, is Associated With Itch in Psoriatic Skin2012
Author(s)
Kou K, Nakamura F, Aihara M, Chen H, Seto K, Komuri-Yamaguchi J, Kambara T, Nagashima Y, Goshima Y and Ikezawa Z
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Journal Title
Acta Derm Venereol
Volume: 92(Accepted)
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[Journal Article] Genome-wide association study identifies HLA-A* 3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population2011
Author(s)
Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M, Shirakata Y, Ikezawa Z, Iijima M, Shiohara T, Hashimoto K, Kamatani N, Nakamura Y
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Journal Title
Hum Mol Genet.
Volume: 20(5)
Pages: 1034-1041
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[Journal Article] A Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis2010
Author(s)
Ikezawa Z, Komori J, Ikezawa Y, Inoue Y, Kirino M, Katsuyama M, Aihara M
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Journal Title
Allergy, Asthma & Immunology Research
Volume: 2(4)
Pages: 235-246
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[Journal Article] Molecular cloning, expression, and characterization of a major 38-kd cochineal allergen2009
Author(s)
Ohgiya Y, Arakawa F, Akiyama H, Yoshioka Y, Hayashi Y, Sakai S, Ito S, Yamakawa Y, Ohgiya S, Ikezawa Z, Teshima R.
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Journal Title
J Allergy Clin Immunol
Volume: 123(5)
Pages: 1157-1162
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[Presentation] What's new in severe drug eruptions2011
Author(s)
Zenro Ikezawa, Yuko Ikezawa, Setsuko Matsukura, Michiko Aihara
Organizer
What's New session on 27th, the 22^<nd> World Congress of Dermatology 2011(WCD 2011)
Place of Presentation
Convention and Exhibition(COEX) Center, Seoul
Year and Date
20110524-29
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[Presentation] Drug-induced urticaria and angioedema in Japan2011
Author(s)
Zenro Ikezawa, Maki Moriya, Kanako Izumi, Hiroko Kunimi, Yuko Ikezawa, Setsuko Matsukura, Michiko Aihara
Organizer
Symposium" Urticarial Syndromes and Angioedema" on 25th, the 22nd WCD 2011
Place of Presentation
Convention and Exhibition(COEX) Center, Seoul
Year and Date
20110524-29
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