Department of Dermatology, Korea University Medical Center, Seoul, South Korea.
Rheumatol Int. 2010 Jun;30(8):1121-4. doi: 10.1007/s00296-009-1342-4. Epub 2010 Jan 6.
Autoinflammatory Blau syndrome (BS) is associated with NOD2 gene mutations that lead to constitutive NFkappaB activation. NOD2 functions as an intracellular receptor for the muramyl dipeptide (MDP) component of peptidoglycan (PGN). The objectives of this study are to analyse whether NFkappaB activation in BS affects immune cell functions, and whether NOD2 and toll-like receptor (TLR) pathways interact. Peripheral blood mononuclear cells (MNCs) from a BS patient and three normal donors were analyzed for their ability to produce pro- and anti-inflammatory cytokines in the presence and absence of MDP, PGN, and lipopolysaccharide (LPS). The results obtained showed that the basal TNF-alpha and IL-10 production by MNCs over 24 h of incubation was very low for both the patient and the normal donors. However, upon stimulation with MDP, LPS, and PGN, the cells from the BS patient produced much lower levels of TNF-alpha, IL-10, G-CSF, and IFN-gamma than the normal donor cells. We conclude that the pathogenic mechanism responsible for the chronic inflammation that characterizes BS may relate to the impaired production of both pro- and anti-inflammatory cytokines to stimuli. The NOD2 pathway possibly interacts with either the TLR2 or TLR4 pathways.
自身炎症性 Blau 综合征 (BS) 与 NOD2 基因突变相关，这些突变导致 NFkappaB 的组成性激活。NOD2 作为肽聚糖 (PGN) 中 muramyl dipeptide (MDP) 成分的细胞内受体发挥作用。本研究的目的是分析 BS 中 NFkappaB 的激活是否会影响免疫细胞的功能，以及 NOD2 和 Toll 样受体 (TLR) 途径是否相互作用。分析了来自 BS 患者和三名正常供体的外周血单核细胞 (MNC) 在存在和不存在 MDP、PGN 和脂多糖 (LPS) 的情况下产生促炎和抗炎细胞因子的能力。结果表明，BS 患者和正常供体的 MNC 在孵育 24 小时后，TNF-alpha 和 IL-10 的基础产生量非常低。然而，在用 MDP、LPS 和 PGN 刺激后，BS 患者的细胞产生的 TNF-alpha、IL-10、G-CSF 和 IFN-gamma 水平明显低于正常供体细胞。我们得出结论，导致 BS 特征性慢性炎症的致病机制可能与对刺激物的促炎和抗炎细胞因子产生受损有关。NOD2 途径可能与 TLR2 或 TLR4 途径相互作用。
