| Project/Area Number |
11670454
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | JICHI MEDICAL SCHOOL |
|---|
Principal Investigator |
MINOTA Seiji JICHI MEDICAL SCHOOL, DEPARTMENT OF MEDICINE, PROFESSOR, 医学部, 教授 (30211593)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | systemic lupus erythematosus / autoantibody / MRL / lpr mouse / NZB / NZW F1 mouse / anti-DNA antibody / anti-nucleolin antibody / 1prマウス |
|---|
| Research Abstract |
To elucidate the autoantigen against which autoantibodies are produced in the earliest phase of the disease process of systemic lupus erythematosus (SLE), serum samples were collected individually and serially from 10 NZB/NZW F1 and 10 MRL/lpr mice. Using immunoblots with mouse thymoma cell (EL-4) lysates as substrates, all mice were found to generate autoantibody against either 150kDa. 110kDa, 75kDa or 55kDa molecule as early as 4 weeks. Anti-DNA antibodies occurred almost at the same time or after those against these four molecules. The number of antigens reactive with autoantibodies in immunoblots increased gradually with age. Antibodies against histone molecules were produced after 8 weeks of age. Among the four antigens, the 110kDa molecule was identified as nucleolin, which is an abundant nucleolar phosphoprotein. Nucleolin binds DNA, RNA and nucleic-acid binding proteins such as histone H1. Nucleolin is a target of granzyme A of cytotoxic T cells, and autoantibodies against it are found in sera from patients with SLE as well as those with various viral infections. These results indicate that nucleolin is one of the immunodominant molecules which break down self-tolerance and initiate autoantibody-spreading in mouse model of SLE.
|
