| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
Oxidized galectin-1 (GAL-1/0x) stimulates macrophages to promote axonal regeneration in peripheral nerves after nerve injury. But, the mechanism of GAL-1/0x, how to regulate macrophages, remains to be clarified. Here we demonstrated effects of GAL-/Ox on mRNA expression of four injury related molecules, interleukin-1β (IL-1β), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and inducible NO synthase (iNOS) in cultured rat peritoneal macrophages. RT-PCR analysis revealed that IL-6 as well as iNOS mRNA expressions were up-regulated by the treatment with 1 ng/ml GAL-1/0x, but the other mRNA did not show significant differences by the application of GAL-1/0x. Increased IL-6 may promote axonal regeneration in peripheral nerves, but up-regulated iNOS, promoting oxidization, may damage regenerating nerves. This problem was resolved by the following experiments. Using lipopolysaccharide (LPS) is one of the typical substance to stimulate macrophages to promote mRNA expressions of cytoki
… More
nes and iNOS. When 10 to 100 ng/ml LPS was applied to cultured macrophages, mRNA expressions of IL-1β, IL-6, LIF, and iNOS were up-regulated. The treatment of 1 ng/ml GAL-1/0x reduced their expressions. This inhibition by GAL-1/0x treatment reduced with decreasing its concentration to 0.1 ng/ml and 0.01 ng/ml GAL-1/0x showed no significant inhibitory effect. These results indicate the possibility that GAL-1/0x regulates expressions of IL-1β, IL-6, LIF, and iNOS to a suitable level, otherwise damaging injured tissues in an excess. Since it has been proved that galectin-1 locates as a reduced form in neurons, their axons, and Schwann cells in injured peripheral nerves and is secreted into extra-cellular space to change into oxidized galectin-1 after oxidization, GAL-1/0x may restrict macrophages to secrete the factors in a proper amount resulting with the promotion of recovery. Since GAL-1/0x, macrophage, and LPS are commonly seen in general inflammation, GAL-1/0x is expected to improve inflammation. Less
|
