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Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-κB (NF-κB), pyrrolidine dithiocarbamate
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kitamei, Hirokuni Iwabuchi, Kazuya Namba, Kenichi Yoshida, Kazuhiko Yanagawa, Yoshiki Kitaichi, Nobuyoshi Kitamura, Mizuki Ohno, Shigeaki Onóe, Kazunori |
| Copyright Year | 2006 |
| Abstract | Experimental autoimmune uveoretini- tis (EAU) is a T helper type 1 cell-mediated auto- immune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/ macrophage lineage and retinal antigen (Ag)-spe- cific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cyto- kines and various stimuli activate a transcriptional factor, nuclear factor- B( NF-B), which modu- lates inflammation and enhances immune re- sponses. In the present study, the therapeutic ef- fect of administration of a NF-B inhibitor, pyrro- lidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ame- liorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor and inter- leukin-1 were suppressed in eyes of PDTC- treated EAU mice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocul- tured, these T cells showed the same level of pro- liferation as those from control mice. Further- more, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abro- gated the T cell-proliferative response and cyto- kine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibi- tory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-B pathway in the le- sion could be a novel target for the successful control of uveoretinitis. J. Leukoc. Biol. 79: 1193-1201; 2006. |
| Starting Page | 1193 |
| Ending Page | 1201 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| DOI | 10.1189/jlb.0805453 |
| Volume Number | 79 |
| Alternate Webpage(s) | http://www.jleukbio.org/content/79/6/1193.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1189/jlb.0805453 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
