2001 Fiscal Year Final Research Report Summary
Regulatory mechanisms of neuro-endocine-immune system in the skin
| Project/Area Number |
12470178
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Nagasaki University |
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Principal Investigator |
KATAYAMA Ichiro Nagasaki University, School of Medicine, Professor, 医学部, 教授 (80191980)
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| Co-Investigator(Kenkyū-buntansha) |
TAKENAKA Motoi Nagasaki University, School of Medicine Hospital and Clinics, Assistant, 医学部・附属病院, 助手 (30281207)
SHIMIZU Kazuhiro Nagasaki University, School of Medicine Hospital and Clinics, Lecturer, 医学部・附属病院, 講師 (80170968)
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| Project Period (FY) |
2000 – 2001
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| Keywords | atopic dermatitis / allergy / histamine / cytokine / chemokine / eosinophil / substance P / stress |
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| Research Abstract |
The number of patients suffering allergic diseases, especially atopic dermatitis has been increasing in recent Japan. Dysfunction of skin barrier, shift to Th2 immune response with elevated serum IgE and abnormal response to mental and/or physical stress are thought to be important etiological and exacerbating factors. It was well known that mediators causing itch in inflamed skin is histamine, prostaglandin and tachykinins. Among these, substance P (SP) plays central role to mediate peripheral itch sensation. We have recently found that SP can be released from epidermal keratinocytes or fibroblasts. To clarify stress response on Th2 allergic inflammations, we conducted the effect of SP, histamine on IL4-induced Th2 chemokines, especially eotaxin production by fibroblasts derived from skin lesions of atopic dermatitis under informed consent.
We observed that SP and histamine increased synergistically eotaxin production and mRNA expression when stimulated with IL-4. We also proved that the expression of IL-4 receptor in fibroblasts stimulated with IL-4 and SP and /or histamine was increased rather than stimulated with IL-4 alone by RT-PCR and FAGS analysis.
This elevated IL4-R expression by SP or histamine was significantly higher and persisted to passage 9 in AD-derived fibroblasts than in normal controls. Whether this aberrant phenomenon was intrinsic or acquired in AD is not clarified in this project. The skin residents cells provide some important roles through the shift to Th2 immune response in AD. Polymorphisms of IL-4R, NK1-R, or H1/H2R genes and their relationship to accerelated Th2 ehemokine production should be studied in the future work for the order made medicine in the future.
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