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C.–H. Yang, I.–M. Fang, C.–M. Yang, C.–P. Lin, M.–S. Chen; Effects of NF–B Inhibitor, Pyrrolidine Dithiocarbamate, on Experimental Autoimmune Anterior Uveitis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):556.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the effect of pyrrolidine dithiocarbamate (PDTC), a nucler factor (NF)–ΚB inhibitor, on chemokine and chemokine receptors expression and thus to elucidate the role of NF–ΚB in experimental autoimmune anterior uveitis (EAAU). Methods: Uveitis was induced in the Lewis rats with injection of melanin–associated antigen into the left footpad. PDTC (40mg/kg/day) was administrated intraperitoneal daily or every two days before the disease onset. The clinical inflammatory activity was recorded daily and scored. Ocular tissues were examined with immunohistochemical stain. NF–ΚB–DNA binding activity of iris/ciliary body tissues was evaluated by electrophoretic mobility shift assay. Gene expression profiles of chemokine and chemokine receptors were examined with semi–quantitative RT–PCR methods. Results: Rats with EAAU had markedly activated NF–ΚB–DNA binding activity in iris/ciliary body. PDTC administration effectively inhibited NF–ΚB–DNA binding activity. PDTC also markedly inhibited the expressions of chemokine genes: monocyte chemoattractant protein (MCP)–1, regulated–upon–activation normal T–cell expressed and secreted (RANTES), interleukin (IL)–8 and chemokine receptors genes: CCR2, CCR5, CXCR3, which subsequently led to dramatically attenuation of the clinical scores, and monocyte/lymphoctye infiltration in rats with EAAU. Conclusions: These studies have established the roles of NF–ΚB in the transcriptional control of MCP–1, RANTES and IL–8 gene in EAAU. Activation of NF–ΚB appears to play an important role in the pathogenesis of EAAU and inhibitors of NF–ΚB activation may have therapeutic importance in acute anterior uveitis.
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