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Nadine Tuaillon, De Fen Shen, Ravi B. Berger, Bao Lu, Barrett J. Rollins, Chi-Chao Chan; MCP-1 Expression in Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2002;43(5):1493-1498.
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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-1α, IL-1β, IL-6, IFN-γ, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1α, 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-γ, IL-6, TNF-α, β-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-γ 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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