| Project/Area Number |
07670972
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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 | Kinki University |
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Principal Investigator |
YAMADA Hidekazu Kinki University of Medicine lecture, 医学部, 講師 (30220396)
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| Co-Investigator(Kenkyū-buntansha) |
TEZUKA Tadashi Kinki University of Medicine Professor, 医学部, 教授 (20013964)
YUDATE Tatsuo Kinki University of Medicine Asisstant, 医学部, 講師 (50288908)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Atopic dermatitis / GVHD / eosinophil / Gm-CSF / Colitis / RANTES / TNFalpha / Keratinocyte / RANTES / TNF α / IFN γ / 大腸 / 皮膚 / T細胞抗原レセプター / サイトカイン / アトピー性皮膚炎 / 大腸菌 / 乾癬 / TNF / スーパー抗原 |
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| Research Abstract |
Patients with atopic dermatitis (AD) sometimes have intercurrent asthma or rhinitis, suggesting the presence of generalized allergic disease. To investigate abdominal symptoms and colonic disorders in patients with AD,we studied 31 adult patients with severe AD.Twenty-two of 31 patients exhibited endoscopic evidence of colitis. Histologically, all patients had evidence of colitis characterized by a marked eosinophilic infiltration. Peripheral eosinophilia and high serum LDH and IgE levels were present in patients with AD and colitis. Quantitative RT-PCR of TNFalpha revealed high expression of TNFalpha mRNA in colonic and skin biopsy specimens from patients with AD-associated colitis compared to control patients. We investigated the mechanisms of eosinophil chemotaxis in atopic dermatits by examining the effect of stimulation of epidermal keratinocytes (KC) by inflammatory cytokines, IFN-_<gamma> and / or TNF-_<alpha>, on the production of eosinophils chemotactic factors. Simultaneous a
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ddition of IFN-_<gamma> and TNF-_<alpha> to cultured keratinocytes synergistically increased eosinophils chemotaxis and the expression of RANTES mRNA and protein level on these cells. Our results indicate that the production of RANTES by keratinocytes may help to explain eosinophil infiltration into the skin in atopic dermatitis. We compared the effect of biological response modifiers (BRM) on development of skin lesions, in BMT.Administration of GM-CSF intravenously in five patients who received BMT resulted in atopic-dermatitis-like lesions in two patients with infiltration of neutrophils, eosinophils and lymphocytes around the follicle, without other signs of GVHD in other organ. None of the patients who were not treated with BRM developed acute GVHD (aGVHD). Our data suggest that severe AD is associated with a high prevalence of colitis which may be allergic in etiology. In allergic skin diseases such as atopic dermatitis, eosinophils migrate from the circulation to the skin. These results showed that several cytokines (RANTES,TNFalpha, GM-CSF) from skin eosinophils and pay an important role for AD. Less
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