Project/Area Number |
05670728
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Dermatology
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
IKAI Kouichi Kyoto University, Faculty of Medicine, Associate professor, 医学部, 助教授 (00135568)
|
Co-Investigator(Kenkyū-buntansha) |
TACHIBANA Takao Kyoto University, Faculty of Medicine, Instructor, 医学部, 助手 (40179718)
|
Project Period (FY) |
1993 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | Atopic Dermatitis / Immunological abormality / Eicosanoid / Leukotriene B4 / LTA4 hydrolase / Lymphocyte / Polymorphonuclear leukocyte / ロイコトリエンB_4 / LTA_4水解酵素 |
Research Abstract |
Leukotrience (LT) B_4 has been suspected to play an important role in the pathogenesis of atopic dermatitis (AD) . LTA_4 hydrolase is the rate-limiting enzyme for LTB_4 biosynthesis. By immunohistochemical study using anti-LTA_4 hydrolase antibody, LTA_4 hydrolase was detected in the cytoplasm of keratinocytes in the epidermis, and in fibroblasts, infiltrating and endothelial cells in the dermis of normal human skin. LTA_4 hydolase activity was detected in human keratinocytes and peripheral leukocytes using HPLC.We examined the LTA_4 hydrolase activity in the peripheral leukocytes of AD patients. The patients were divided into three categories (severe, moderate and mild) on the basis of clinical severity. The LTA_4 hydrolase activity in the supernatant fraction of polymorphonuclear leukocytes (PMN) was significantly higher in severe AD patients (123.94<plus-minus>15.92 unit) than in moderate (49.03<plus-minus>9.12 unit) and mild (28.74<plus-minus>10.70 unit) AD and normal controls (15.14<plus-minus>1.67 unit) . The peripheral blood mononuclear cells showed higher LTA_4 hydrolase activities in severe AD patients than in moderate and mild AD patients and normal controls. LTA_4 hydrolase activity in PMN was reduced after improvement of eczema in several patients with severe or moderate AD.This study should provide new insights into the pathophysiological role of LTA_4 hydrolase in AD,and possible new strategies for the treatment of this disease.
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