1999 Fiscal Year Final Research Report Summary
Analysis of the physiologic roles of secretory leukoprotease inhibitor (SLPI) in airway inflammation by manipulating the murine SLPI gene
| Project/Area Number |
09557054
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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 | 展開研究 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
WATANABE Akira Institute of Development, Aging and Cancer (IDAC), Tohoku University, Associate Professor, 加齢医学研究所, 助教授 (70220861)
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| Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Toshiaki IDAC, Tohoku University, Instructor, 加齢医学研究所, 助手 (10280926)
YAEKASHIWA Masahiro IDAC, Tohoku University, Instructor, 加齢医学研究所, 助手 (70261477)
MASUDA Ken-ichi Teijin, Investigator, 創薬第二研究所, 主任研究員
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| Project Period (FY) |
1997 – 1999
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| Keywords | SLPI / cDNA and gene expression / tissue distribution / airway inflammation / in situ hybridization / gene structure / gene targeting / chromosomal localization |
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| Research Abstract |
Secretory leukoprotease inhibitor (SLPI) is a 12-kD serine protease inhibitor found in the mucus mainly in respiratory tract and genital glands. The function of SLPI was first thought to protect the tissues form excessive destruction by counterbalancing the neutrophil elastase activity released during inflammation. However, recent studies have revealed that SLPI is produced by alveolar macrophages, monocytes and granulocytes as well as by serous cells in the mucous glands and that this protein exerts diverse functions such as antagonism to LPS-elicited signal transduction in alveolar macrophages and inhibition of cyclooxygenase-2 resulting in suppression of prostagalndin E2 and matrix metalloproteinases in monocytes.
Based on these observations, we considered gene targeting the most effective strategy to elucidate the function(s) of SLPI. For this purpose, we cloned to mouse SLPI cDNA and then the entire mouse gene. The cDNA was used to examine the SLPI gene expression in mice in terms of tissue distribution and changes during inflammation as well as to screen the mouse genomic lirary.
The targeting vector was constructed and introduced into embryonic stem cells.
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