MCP-1 expression in endotoxin-induced uveitis.
OBJECTIVE
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-1alpha, IL-1beta, IL-6, IFN-gamma, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1alpha, 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-gamma, IL-6, TNF-alpha, beta-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-gamma 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.
Tuaillon
Nadine
N
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg. 10 Room 10-N-103, 10 Center Drive, Bethesda, MD 20892-1857, USA.
Shen
De Fen
DF
Berger
Ravi B
RB
Lu
Bao
B
Rollins
Barrett J
BJ
Chan
Chi-Chao
CC
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D018932:Chemokine CCL2; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger