RGD Reference Report - Depletion of MCP-1 increases development of herpetic stromal keratitis by innate immune modulation. - Rat Genome Database

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Depletion of MCP-1 increases development of herpetic stromal keratitis by innate immune modulation.

Authors: Kim, B  Sarangi, PP  Lee, Y  Deshpande Kaistha, S  Lee, S  Rouse, BT 
Citation: Kim B, etal., J Leukoc Biol. 2006 Dec;80(6):1405-15. Epub 2006 Sep 22.
RGD ID: 8548890
Pubmed: (View Article at PubMed) PMID:16997857
DOI: Full-text: DOI:10.1189/jlb.0406295

Chemokines are important chemoattractant inflammatory molecules, but their interdependent network in disease pathogenesis remains unclear. Studies in mouse models have shown that herpetic stromal keratitis (SK) is produced by the consequence of a tissue-destructive immunoinflammatory reaction involving herpes simplex virus type 1 (HSV) infection. Here we found that ocular HSV infection leads to increased expression of monocyte chemoattractant protein-1 (MCP-1), one of the major chemoattractants for immune cells that express CCR2, in the SK cornea. However, MCP-1 is unlikely to be a chemoattractant for infiltrating Gr-1(+), CD11b(+) cells in SK, as these cells are found to be CCR2 negative. Nevertheless, infection of MCP-1(-/-) mice resulted in more severe SK lesion severity compared with WT mice (P<0.01). We demonstrated that the loss of MCP-1 in the SK cornea caused a significant overexpression of macrophage inflammatory protein-2 (MIP-2) (P<0.01) on days 2 and 4 postinfection and increased infiltration of inflammatory cells (Gr-1-high and CD11b(+)) expressing CXCR2, a receptor for MIP-2, into the cornea. Subsequently, increased infiltration of inflammatory cells accelerated by MIP-2 overexpression might result in the high production of inflammatory molecules, including vascular endothelial growth factor (VEGF) and IL-1beta in SK, as well as CpG oligodeoxynucleotide (ODN)-implanted eyes of MCP-1(-/-) mice. These results indicate that MCP-1 in the SK cornea might regulate the expression of other chemokines, as well as the infiltration of inflammatory cells and control development of SK.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (chemokine (C-C motif) ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information