2004 Fiscal Year Final Research Report Summary
Pathogenic role of virus gene that was detected in patients with rheumatoid arthritis
| Project/Area Number |
15591043
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
膠原病・アレルギー・感染症内科学
|
|---|
| Research Institution | TOHOKU UNIVERSITY |
|---|
Principal Investigator |
MUNAKATA Yasuhiko TOHOKU UNIVERSITY, HOSPITAL, RESEARCH ASSOCIATE, 病院, 助手 (20271950)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAMEOKA Junichi TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学系研究科, 助教授 (30261621)
HARIGAE Hideo TOHOKU UNIVERSITY, HOSPITAL, LECTURER, 病院・講師 (50302146)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Parvovirus B19 / NS1 / rheumatoid arthritis / TNF-α |
|---|
| Research Abstract |
Human parvovirus B19 (B19) often causes acute polyarthritis in adults. We analyzed nucleotide sequences of the B19 genome of patients with rheumatoid arthritis (RA), and then introduced the nonstructural protein 1 (NS1) gene of B19 into C57BL/6 mice that had a genetic origin not susceptible to arthritis. The transgenic mice developed no lesions spontaneously, but were susceptible to type II collagen (C II )-induced arthritis. B19 NS1 was expressed in synovial cells on the articular lesions that were histologically characten NS1 transgenic mice to the same levels as those of DBA/1 mice, which werendicating that a nonpermissive H-2b haplotype in the wild type of C57BL/6 can be made susceptible to polyarthritis through the expression of NS1. This study is the first to show that a viral agent from the joints in humans can cause C II-induced arthritis resembling RA. B19 protein, DNA and RNA were detectable repeatedly at different times in macrophages, T and B cells in the rheumatoid synovium, indicating persistent activation of B19 in the RA synovium. We also showed that transduction of the macrophage cell line, U937 with NS-1 gene-activated transcription factors, AP-1 and AP-2, resulted in the up-regulation of TNF-α gene expression and secretion of TNF-α from host cells. This indicated the persistent activation of B19 may constantly up-regulate the TNF-α gene in infected cells. NS1 transgenic model leads us to hypothesize that persistently activated B19 may induce an increased immune response, such as activating and proliferating synoviocytes by an autocrine and paracrine pathway in the joints, resulting in an inflammatory process resembling RA.
|
