First Author | Iwata D | Year | 2010 |
Journal | Invest Ophthalmol Vis Sci | Volume | 51 |
Issue | 4 | Pages | 2077-84 |
PubMed ID | 19907030 | Mgi Jnum | J:160409 |
Mgi Id | MGI:4454393 | Doi | 10.1167/iovs.09-4030 |
Citation | Iwata D, et al. (2010) Amelioration of experimental autoimmune uveoretinitis with nuclear factor-{kappa}B Inhibitor dehydroxy methyl epoxyquinomicin in mice. Invest Ophthalmol Vis Sci 51(4):2077-84 |
abstractText | Purpose. Experimental autoimmune uveoretinitis (EAU), a Th1/Th17 cell-mediated autoimmune disease induced in mice, serves as a model of human endogenous uveitis. In this model, proinflammatory cytokines and various stimuli activate the transcriptional factor, nuclear factor-kappaB (NF-kappaB), in the retina. The therapeutic effect of the NF-kappaB inhibitor, dehydroxy methyl epoxyquinomicin (DHMEQ), was examined on EAU. Methods. EAU was induced in B10.BR mice by K2 peptide immunization. DHMEQ (40 mg/kg/d) was administered daily by intraperitoneal injection. Clinical severity and histopathologic severity were assessed. Translocation of NF-kappaB p65 into the nucleus in EAU retina was assessed. T cells were collected from draining lymph nodes of the K2-immunized mice to examine antigen (Ag)-specific T-cell active responses and cytokine production in vitro. Results. Disease onset was significantly delayed in DHMEQ-treated mice (15.6 days) compared with untreated mice (12.6 days; P < 0.01). Histologic severity was significantly milder in DHMEQ-treated mice (score, 1.13) than in controls (score, 2.33; P < 0.05). DHMEQ suppressed the Ag-specific T-cell active responses and downregulated the productions of Th-1 type cytokines in vitro in a dose-dependent manner. Alternation was not observed in Th-2 type cytokines. Pretreatment of primed T cells or Ag-presenting cells with DHMEQ reduced T-cell activation and Th1/Th17 cytokine production. DHMEQ treatment suppressed the translocation of the NF-kappaB p65 subunit into the nuclei. Conclusions. Systemic administration of DHMEQ suppressed NF-kappaB translocation in the retina, which might have reduced the inflammation of ocular tissues. DHMEQ-mediated regulation of NF-kappaB p65 could be a therapeutic target for the control of endogenous ocular inflammatory diseases. |