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1 From the National Institutes of Health, National Eye Institute, Bethesda, Maryland; 2 Case Western Reserve University, Cleveland, Ohio; the 3 Children’s Hospital, Harvard Medical School, Boston, Massachusetts; and the 4 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
PURPOSE. Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with chemoattractant properties for monocytes, memory T cells, natural killer cells, mast cells, and basophils. To delineate the role played by MCP-1 in acute anterior uveitis, a common ocular inflammation, MCP-1-/- mice and wild-type matched control mice were analyzed for the development of endotoxin-induced uveitis (EIU) in response to subcutaneous injection of a sublethal dose of lipopolysaccharide (LPS).
METHODS. EIU was induced in MCP-1-/- and wild-type control mice by a single subcutaneous injection of Salmonella typhimurium LPS endotoxin at day 0. Alternatively, MCP-1-/- mice were injected subcutaneously with LPS plus recombinant MCP-1 at day 0 and with recombinant MCP-1 6 hours later. Mice were killed at day 1 or 3 after injection. Serum levels of IL-1
, IL-1ß, IL-6, IFN-
, TNF-, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1, MIP-2, regulated on activation normal T-cell expressed and secreted (RANTES), and MCP-1 were determined by ELISA. Eyes were collected and analyzed histologically and by RT-PCR for MCP-1, IFN-, IL-6, TNF-, ß-actin, MCP-5, RANTES, KC, inflammatory protein (IP)-10, and toll-like receptor (TLR)-4.
RESULTS. EIU was strongly reduced in MCP-1-/- mice compared with wild-type control mice. The number of ocular inflammatory cells was significantly reduced. Moreover, intraocular IFN- transcription was increased. EIU was induced in MCP-1-/- mice by co-administration of recombinant rat MCP-1 and LPS.
CONCLUSIONS. Data indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a new therapeutic strategy for acute anterior uveitis.
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