| Co-Investigator(Kenkyū-buntansha) |
池澤 優子 横浜市立大学, 市民総合医療センター, 助教 (80457879)
山口 由衣 横浜市立大学, 医学部, 助教 (60585264)
國見 裕子 横浜市立大学, 附属病院, 助手 (10567605)
秦田 勇二 海洋研, 極限環境生物圏研究センター, グループ・リーダー (20399562)
相原 道子 横浜市立大学, 附属病院, 教授 (90231753)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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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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