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Publications (2)4.94 Total impact

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    ABSTRACT: To characterize the transcriptome of allergic conjunctivitis mediated by eosinophil-related chemokine receptor CCR3 and to identify a candidate for possible therapeutic intervention in eosinophilic inflammation of the eye. Mice were sensitized to ragweed pollen, and allergic conjunctivitis was induced by an allergen challenge. The induction of allergic conjunctivitis was used to determine whether an inhibition of CCR3 would suppress eosinophilic inflammation and the allergen-induced immediate hypersensitivity reaction. In addition, sensitized mice were treated with a CCR3 antagonist or an anti-CCR3 antibody before the allergen challenge. Eosinophilic inflammation was evaluated histologically at 24 hours after the allergen challenge. Transcriptional changes with or without a blockade of CCR3 were determined by microarray analyses. Blockade of CCR3 significantly suppressed allergen-induced clinical signs, mast cell degranulation, and eosinophilic inflammation. Clustering analysis of the transcriptome during the early phase identified clusters of genes associated with distinct biological processes. A CCR2 ligand, monocyte chemoattractant protein (MCP)-1, was identified in the cluster of genes related to mast cell activation. MCP-1, an attractant of monocytes but not eosinophils, was in the top 10 transcripts among the genome and was suppressed by CCR3 blockade. Importantly, antibody blockade of MCP-1 suppressed the eosinophilic inflammation significantly. CCR3 regulates not only the eosinophilic inflammation but also the clinical signs and mast cell degranulation. The CCR3-mediated transcriptome is characterized by many biological processes associated with mast cell activation. Among these CCR3-mediated processes, MCP-1 was found to be significantly involved in eosinophilic inflammation probably by an indirect pathway.
    Investigative ophthalmology & visual science 12/2008; 49(12):5307-13. · 3.43 Impact Factor
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    ABSTRACT: Herpetic stromal keratitis (HSK) is an immunopathological reaction to herpes simplex virus type 1 (HSV-1) corneal infection. It has been reported that CD4+ cells play the most important role in the pathogenesis of this disease. In this study, we have focused on two chemokine receptors, CCR5 and CXCR3, which are expressed on CD4+ Th1 cells in mice HSK model. CCR5-deficient (CCR5KO), CXCR3-deficient (CXCR3KO), CCR5/CXCR3 double-deficient (DKO), and wild type (WT) mice (C57/BL6 background) were infected intracorneally with HSV-1 (CHR3 strain). The corneas were examined biomicroscopically, and cryosections of the corneas were examined histologically and immunohistochemically. Real-time RT-PCR and RNase protection assay (RPA) were performed, and the virus titers were measured in excised eyes and trigeminal ganglia (TG). The HSK clinical severity in DKO mice was significantly lower than that in WT mice, and this was reversed by transfer of cells from the spleen of WT mice to DKO mice. Histologically, the numbers of T cells (CD4+ and CD8+ cells) and neutrophils infiltrating the cornea were significantly fewer in CCR5KO, CXCR3KO, and DKO mice. Transcript levels of immune-related cell surface marker in the eye by RPA were reduced in DKO mice. The expression of I-TAC was significantly increased in the cornea of CCR5KO mice, and MIP-1alpha and MIP-1beta were significantly lower in CXCR3KO mice than in WT mice by RT-PCR. There were no significant differences of virus titers in the eye and TG among any groups of mice except the increase in the TG of DKO mice on day 5 PI. The suppression of chemotaxis and activation of CD4+ Th1 cells by the lacking of CXCR3 and CCR5 causes a decrease of other infiltrating cells, resulting in a lower severity of HSK. These results suggest that targeting chemokine receptors is a promising way to treat HSK.
    Current eye research 10/2008; 33(9):736-49. · 1.51 Impact Factor