| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Research Abstract |
Monocyte chemoattractant protein-1(MCP-1,CCL2) is a well-defined CC chemokine implicated in the pathology of various types of brain injuries, such as ischemic and traumatic injuries. Previously, we demonstrated that MCP-1 production was upregulated in the dorsal root ganglia (DRG) of neuropathic pain model rats. In this study, we carried out the double immunofluorescent staining between MCP-1 and activating transcription factor-3(ATF3) to examine whether MCP-1 was produced in the injured or uninjured DRG neurons after the nerve ligation. In the small-sized neurons (cell body area <600 μm^2), MCP-1-immunoreactivity (ir) was observed not only in the injured neurons, but also in the uninjured ones. On the other hand, in the large-sized neurons (>1200μm^2), almost all of the MCP-1-ir neurons were ATF3-ir-positive. This result suggests that intercellular interaction between the injured and uninjured neurons is involved in the MCP-1 upregulation in the small-sized DRG neurons.
Furthermore, we investigated the effects of adenosine 5'-O-(3-thiotriphosphate)(ATPγS) on MCP-1 production using the rat cortico-striatal slice culture. ATPγS induced MCP-1 mRNA expression and protein production in astrocytes. The involvement of MAP kinases in this induction was examined by using several kinds of MAP kinase inhibitors. PD98059 and U0126, MEK inhibitors, significantly suppressed ATPγS-induced MCP-1 mRNA expression and protein production. Inhibition of JNK by SP600125 resulted in a partial suppression of them. On the other hand, SB203580, a p38 MAP kinase inhibitor, significantly enhanced ATPγS-induced MCP-1 productfon. Further investigation revealed that SB203580 extended the duration of MCP-1 mRNA expression induced by ATPγS and thereby increased the net production of MCP-1. These results demonstrate the reciprocal regulation of ATPγS-induced MCP-1 production by ERK and p38 MAP kinases in astrocytes.
|
