Higher Expression of NOD1 and NOD2 is Associated with Vogt-Koyanagi-Harada (VKH) Syndrome But Not Behcet's Disease (BD)

• Published in: Current molecular medicine Vol. 16; no. 4; p. 424
• Main Authors: Deng, B, Ye, Z, Li, L, Zhang, D, Zhu, Y, He, Y, Wang, C, Wu, L, Kijlstra, A, Yang, P
• Format: Journal Article
• Language: English
• Published: Netherlands 01-05-2016
• Subjects: Adult; Behcet Syndrome - genetics; Biomarkers - metabolism; Cell Proliferation; Cytokines - metabolism; Dendritic Cells - metabolism; Female; Gene Expression Regulation; Humans; Inflammation Mediators - metabolism; Leukocytes, Mononuclear - metabolism; Male; Nod1 Signaling Adaptor Protein - genetics; Nod1 Signaling Adaptor Protein - metabolism; Nod2 Signaling Adaptor Protein - genetics; Nod2 Signaling Adaptor Protein - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Uveomeningoencephalitic Syndrome - genetics
• ISSN: 1875-5666
• DOI: 10.2174/1566524016666160316153038

NOD1 and NOD2 have been found to play a significant regulatory role in autoimmune disease. To analyze the role of NOD1 and NOD2 in the pathogenesis of Vogt- Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD). We analyzed the expression of NOD1 and NOD2 from PBMCs by RT-PCR and Western Blot. PBMCs and DCs were cultured with NOD receptor ligands iE-DAP (NOD1) or MDP (NOD2) and cells and supernatants were analyzed by flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA). DCs and CD4+T cells were co-cultured with or without stimulation and cells and supernatants were analyzed by FCM and ELISA. A higher expression of NOD1 and NOD2 was observed in patients with active VKH syndrome as compared with controls. However, no significant differences were found between BD patients and controls. Activation of NOD1 and NOD2 with iE-DAP or MDP markedly increased the level of IL-6, TNF-α and IL-1β in PBMCs and DCs and induced the expression of CD40, CD80, CD83, CD86 and HLA-DR on DCs. Activation of NOD1 and NOD2 in DCs promoted the differentiation and proliferation of CD4(+)T cells. In conclusion, activation of NOD1 or NOD2 increased the production of pro-inflammatory cytokines in PBMCs and promoted the maturation and activation of human DCs in association with stimulation of Th1 and Th17 cells. Our results suggest that over-expression of NOD1 and NOD2 may be involved in the pathogenesis of VKH syndrome.