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Graefes Arch Clin Exp Ophthalmol ; 248(12): 1737-47, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20585797

RESUMO

BACKGROUND: To demonstrate the expression of lymphotactin and its receptor (XCR) in the iris/ciliary body and popliteal lymph node, and to clarify their roles in experimental autoimmune anterior uveitis (EAAU). METHODS: Uveitis was induced in Lewis rats by injection of melanin-associated antigen into the peritoneum and footpad. At defined time points, mRNA expression levels of lymphotactin and XCR in the iris/ciliary body and popliteal lymph node were measured by semiquantitative polymerase chain reaction. Lymphotactin levels in aqueous humor and serum after immunization were determined by enzyme-linked immunosorbent assay. In a separate experiment, an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), was injected daily into the intraperitoneum after immunization. Cellular sources of lymphotactin were determined by immunhistochemical staining and flow cytometry. RESULTS: Lymphotactin mRNA was upregulated in the iris/ciliary body with a peak level at day 14, which is in line with the disease course. XCR mRNA was expressed maximally and then declined gradually from days 5 to 21. With an expression pattern similar to that of mRNA expression, lymphotactin in aqueous humor had attracted corresponding numbers of leukocytes. PDTC markedly inhibited the expression of lymphotactin in aqueous humor and serum. Immunohistochemical staining and flow cytometry analysis revealed that the expression of lymphotactin was detected in infiltrated inflammatory cells, dominantly CD8+ T cells, and increased along with inflammation. CONCLUSIONS: The lymphotactin and XCR interaction might direct distinct lymphocytes subsets to inflammatory sites. Lymphotactin could regulate the inflammatory process. Lymphotactin expression may be modulated, at least in part, through the NF-κB signaling pathway.


Assuntos
Doenças Autoimunes/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Linfocinas/genética , Receptores CXCR/genética , Sialoglicoproteínas/genética , Uveíte Anterior/genética , Animais , Humor Aquoso/metabolismo , Doenças Autoimunes/metabolismo , Corpo Ciliar/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Técnicas Imunoenzimáticas , Iris/metabolismo , Linfonodos/metabolismo , Linfocinas/metabolismo , NF-kappa B/antagonistas & inibidores , Reação em Cadeia da Polimerase , Prolina/análogos & derivados , Prolina/farmacologia , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos Lew , Receptores CXCR/metabolismo , Sialoglicoproteínas/metabolismo , Tiocarbamatos/farmacologia , Regulação para Cima , Uveíte Anterior/metabolismo
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