Caccamo Daniela, Ferlazzo Nadia, Currò Monica, Ricca Sergio, Ientile Riccardo
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98123 Messina, Italy.
Med Sci (Basel). 2018 Nov 16;6(4):103. doi: 10.3390/medsci6040103.
Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires an optimal vitamin D status, we aimed to assess the involvement of TG2/NF-κB signaling in cytokine production in PBMC isolated from adult subjects with different vitamin D status. We observed TG2 up-regulation and a significant positive correlation between TG2 expression and tumor necrosis factor (TNF)-α mRNA levels in PBMC of recruited patients. The mRNA levels of TG2 and TNF-α were higher in PBMC of subjects having hypovitaminosis D, namely plasma 25(OH)vitamin D3 levels lower than 50 nmol/L, than in those with normal vitamin D levels. Moreover, NF-κB up-regulation and nuclear translocation were detected, concomitantly with TG2 as well as TNF-α increased expression, in PBMC of vitamin D-deficient subjects. The present findings confirm that an increase in TG2 expression exacerbates the activation of NF-κB and the production of pro-inflammatory cytokines, and suggest a link between vitamin D deficiency, TG2 up-regulation, and inflammation.
近期证据表明，转谷氨酰胺酶2（TG2）参与适应性免疫反应。外周血单个核细胞（PBMC）已被广泛用于表征免疫反应激活过程中发生的分子机制。鉴于免疫系统功能的维持需要最佳的维生素D状态，我们旨在评估TG2/NF-κB信号通路在从具有不同维生素D状态的成年受试者中分离出的PBMC中细胞因子产生过程中的作用。我们观察到招募患者的PBMC中TG2上调，且TG2表达与肿瘤坏死因子（TNF）-α mRNA水平之间存在显著正相关。维生素D缺乏症患者（即血浆25(OH)维生素D3水平低于50 nmol/L）的PBMC中TG2和TNF-α的mRNA水平高于维生素D水平正常的患者。此外，在维生素D缺乏的受试者的PBMC中检测到NF-κB上调和核转位，同时伴有TG2以及TNF-α表达增加。目前的研究结果证实，TG2表达增加会加剧NF-κB的激活和促炎细胞因子的产生，并表明维生素D缺乏、TG2上调和炎症之间存在联系。
