Project/Area Number |
09680703
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cell biology
|
Research Institution | Teikyo University |
Principal Investigator |
KASAI Kenichi Teikyo Univ., Fac.Pharm.Sci., Professor, 薬学部, 教授 (40001052)
|
Co-Investigator(Kenkyū-buntansha) |
ARATA Yoichiro Teikyo Univ., Fac.Pharm.Sci., Asist.Prof., 薬学部 (90246017)
HIRABAYASHI Jun Teikyo Univ., Fac.Pharm.Sci., Lecturer, 薬学部, 講師 (40156691)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | galectin / apoptosis / nematode / C.elegans / lymphocyte / レクチン / マクロファージ |
Research Abstract |
Galectins, proteins of one of animal lectin families, recognize specifically galactoside-containing sugar chains on complex carbohydrates. Recently, a number of observations have been reported on possible involvement of galectins in apoptosis, especially, in cells belonging to the immune system. Apoptosis induced by galectin- I suggests a new triggering mechanism in which Fas does not have any role but recognition of specific sugar chains on cell surface play an important role. We obtained results supporting such a hypothesis by using mouse lymphocytes MHL/lpr which lack Fas. Galectin-1 induced apoptosis of these cells. Galectin-1 also suppressed attachment of T cells to extracellular matrix and release of cytokines. These observations suggested a potential use of galectin-1 for therapeutics of autoimmune diseases. Therefore, its potential was validated in collagen-induced arthritis using gene and protein therapy strategies. An injection of recombinant galectin-1 or fibroblasts engineered to secrete galectin-1 was able to prevent clinical and histopathological manifestations of arthritis. Galectin-1 treatment resulted in an overall reduction in anti-collagen IgG levels. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. On the other hand, we have found that the nematode Caenorhabditis elegans has also galectins very similar to those of mammals. Since this is an excellent system for investigations on the possible relationship between galectins and apoptosis, we cloned more than ten C.elegans genes each of which was found to encode one of galectins, and prepared a variety of modified genes. These genes will be used for various experiments such as preparation of transgenic nematodes and introduction of reporter genes.
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