Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages
Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages
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DOI：
10.1007/s00726-015-2039-5
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发表时间：
2015-11-01
期刊：
影响因子：
3.5
通讯作者：
Ientile, Riccardo
中科院分区：
文献类型：
--
作者：
Matarese, Giovanni;Curro, Monica;Ientile, Riccardo
最近的证据强调，转氨酶2（TG 2），蛋白质交联酶，可能在炎症的早期阶段发挥作用。高水平的TG 2与核因子-κ B（NF-κ B）的组成性激活相关，NF-κ B被认为是炎症的主要调节因子。在这种情况下，NF-κ B配体的受体激活剂（RANKL）和NF-κ B的受体激活剂在调节与不同病理状况相关的细胞因子分泌中具有广泛的功能。表达和分泌骨保护素（OPG）和RANKL的人牙周膜（HPDL）细胞代表了用于监测炎症微环境中的细胞反应（例如牙周炎依赖性组织反应）的有用的“离体”模型。因此，我们评估了TG 2表达和RANKL/OPG比例的变化发生在培养的HPDL细胞。从慢性牙周炎（CP）患者和健康受试者获得HPDL细胞。我们观察到一些炎症标志物，如IL-6，TNF-α，和HMGB-1的上调，并在同一时间增加TG 2 mRNA水平在HPDL细胞从CP患者相比，健康受试者。我们发现CP患者HPDL细胞中RANKL/OPG比值与TG 2 mRNA水平呈正相关。在平行实验中，我们证明TG 2抑制降低了CP患者HPDL细胞和十四酰佛波醇乙酸酯处理分化为巨噬细胞的单核细胞中的RANKL表达。鉴于RANKL在NF-κ B B通路中的关键作用以及观察到的促炎细胞因子的上调，我们的数据表明TG 2可能参与牙周病中发生的炎症反应的分子机制。
Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-kappa B) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-kappa B have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful "ex vivo" model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-alpha, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-kappa B pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease.