SOBUE Gen NAGOYA UNIVERSITY, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20148315)
DOYU Manabu NAGOYA UNIVERSITY, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (90293703)
|Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2003 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2002 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Infiltration of mononuclear cells causes autoimmunodiseases. Chemokines mediate cell migration. In order to understand the pathomechanism of autoimmuno-inflammatory myopathies, such as polymyositis (PM) and dermatomyositis (DM), we investigated the expression of chemokines in muscle tissue.
In 2002,we examined the expression of several chemokines in muscle tissues with many types of muscle diseases. First, we could not detect the expression of any chemokines in normal muscle tissues. Second, we compared expression of chemokines in muscle tissues between PM and DM. At perivascular region, the expression of MCP-1 and MIP-1α were greater in DM than in PM. At interstitial region in DM, MCP-1,MIP-1α, RANTES, and IP-10 were significantly up-expressed compared to that in PM. Furthermore, mononuclear cells expressing CCL2,CCL4,CCL5,and CXCR3,these are chemokine receptors corresponding to those chemokines, gathered at those lesions respectively. This result showed critical roles of those chemokines in the pathogenesis of DM.
In 2003,we paid a lot of attention to chemokine receptors. Some chemokine receptors are known to be expressed on specific mononuclear cells that bear proper roles. CCR3 and CCR4 were expressed on mononuclear cells that play as Th2 cells, and CCR5 and CXCR3 were expressed on Th1 cells. We can know Th1/Th2 balance in muscle tissue by observation of the number of these chemokine receptor expressing cells. By means of this method, we could know that the balance deviated to Th2 in PM, and to Th1 in DM. However, in endomysium it incompletely deviated to Th2 in PM. This result indicated the possibility that the responsibility to therapy in PM is weaker than that in DM. Now, we have the plan to confirm it.