| Project/Area Number |
09670565
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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 |
Gastroenterology
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| Research Institution | THIRD DEPARTMENT OF INTERNAL MEDICINE, OSAKA CITY UNIVERSITY MEDICAL SCHOOL |
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Principal Investigator |
OSHITANI Nobuhide OSAKA CITY UNIVERSITY MEDICAL SCHOOL, THIRD DEPARTMENT OF INTERNAL MEDICINE LECTURER, 医学部, 講師 (20231235)
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| Co-Investigator(Kenkyū-buntansha) |
HATO Fumihiko OSAKA CITY UNIVERSITY MEDICAL SCHOOL, SECOND DEPARTMENT OF PHYSIOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (00198772)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | CLASS II MHC / HLA-DR / ANTIGENIC PEPTIDE / CROHN'S DISEASE / ULCERATIVE COLITIS / TANDEM-MASS ANALYSIS / MASS ANALYSIS / HCADR / class II MHC / HLA-DR / 炎症性腸疾患 / HLA DR |
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| Research Abstract |
The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We isolated HLA-DR-associated peptides from human intestine and sequenced their amino-acid residues by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. Serum antibody titers against two of the above determined antigens were measured. We detected 73 parent proteins from 4 controls, 10 patients with ulcerative colitis, and 10 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 582.2 to 2988.5, representing 7 to 27 amino acid residues. Sixty-eight of these 73 parent proteins were exogenous proteins. Neither MHC nor invariant chain-derived peptides were found among human intestinal class II MHC-associated peptides, contrary to previous findings for transformed cells. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found veryfrequently in patients with inflammatory bowel disease. Serum antibody titers against S.cerevisiae and C.elegans were measured, and were significantly higher in patients with inflammatory bowel disease than in controls. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine are participated with exogenous antigen presentation. Increased immune responses against S.cerevisiae and C.elegans were found in patients with inflammatory bowel and may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.
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