| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Research Abstract |
To investigate the mechanisms of cell infiltration and vascular permeability in acute inflammation, we developed the recombinant rabbit MCP-1 and GRO and their antibodies, together with immunoassay systems. Using rabbit model of arthritis, the production of monocyte chemoattractant protein-1 (MCP-1), its regulation by cytokines and the role of MCP-1 in the recruitment of monocytes were investigated. MCP-1 was detected in synovial fluid (SF) at early inflammatory phase, and synovial lining cells were the main source of MCP-1. The production of MCP-1 was regulated by TNFα and IL-1. IL-8 does not appear to regulate the production of MCP-1. MCP-1 did not regulate the production of TNFα, IL-1 and IL-8. Administration of neutralizing anti-MCP-1 antibody inhibited monocyte infiltration, and administration of MCP-1 induced macrophage influx. Early events associated with neutrophil infiltration appears to be important for MCP-1 to induce a later macrophage influx. Next, we investigated the functional role of growth related protein (GRO). GRO was detected in SF at early inflammatory phase, and synovial lining cells were the main source of GRO.GRO as well as IL-8 are important mediators involved in the recruitment of neutrophils. IL-1 produced in the early phase stimulates GRO production, GRO plays a role in the later induction of IL-1β and IL-1Ra, and induction of GRO is not regulated by IL-8. GRO induced a vascular permeability via inducing the production of TNFα.
|
