The Role of Granulysin in Muscle Fiber Injury in Polymyositis
| Project/Area Number |
16590998
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
OKADA Satoshi Tokyo Dental College, Department of Dentistry, Assistant Professor, 歯学部, 講師 (80194356)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | polymyositis / apoptosis / granulysin |
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| Research Abstract |
Granulysin (GLN) is a cytolytic molecule that co-localizes with perforin in cytolytic T cells. We investigated the role of GLN in the pathogenesis of polymyositis (PM).
Rat myoblast cell line L6 was cultured in RPMI 1640 (10 % FCS), and differentiated to muscle fibers in RPMI 1640 (2% horse serum). Recombinant (r) GLN was co-incubated with L6 or expressed intracellulary, and GLN-mediated cytotoxicity was evaluated by MTT assay. DNA fragmentation was also evaluated by TUNEL assay. Localization of GLN in biopsied muscle specimen (PM,DM and non-inflammatory muscle diseases) was studied by immunofluorescent staining.
rGLN induced cytotoxicity for L6 in a dose dependent manner when it was introduced extracellulary. Intracellular expression of rGLN also damaged L6. DNA fragmentation was observed in L6 in which rGLN was expressed, not in L6 when rGLN was administered extracellulary. Immunofluorescent staining did not show GLN molecules in L6 cytosol when rGLN was co-incubated with L6. In contrast, rGLN was detected in jurkat cytosol in which rGLN induced DNA fragmentation. In biopsied muscle specimens, GLN was localized in CD3 positive cells adjacent to muscle fibers. GLN was not observed inside muscle fibers.
Taken together, GLN may be released from T cells as well as perforin leading to muscle fiber damage, and muscle cells do not uptake GLN so that GLN-mediated apoptosis does not take place.
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Report
(3 results)
Research Products
(3 results)
