TNF 超家族/肿瘤坏死因子受体超家族细胞因子基因在镰状细胞贫血中的表达：在外周血单个核细胞和血浆中上调 TNF 样细胞因子 1A（TL1A）及其诱饵受体（DcR3）。
TNFSF/TNFRSF cytokine gene expression in sickle cell anemia: Up-regulated TNF-like cytokine 1A (TL1A) and its decoy receptor (DcR3) in peripheral blood mononuclear cells and plasma.
机构信息
Mohammed Bin Abdulrahman Al-Omran Scientific Chair for Hematological Diseases Prevalent in the Al-Ahsa Area, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
Mohammed Bin Abdulrahman Al-Omran Scientific Chair for Hematological Diseases Prevalent in the Al-Ahsa Area, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
出版信息
Cytokine. 2019 Nov;123:154744. doi: 10.1016/j.cyto.2019.154744. Epub 2019 Jun 28.
BACKGROUND
Sickle cell anemia (SCA), a disorder with an important inflammatory component, where vasoocclusion is major contributor to the disease pathophysiology. Pro-inflammatory cytokines play an important regulatory role in the process of inflammation. We investigated the expression TL1A/DR3/DcR3 cytokine signaling pathway in peripheral blood mononuclear cells (PBMC) and their corresponding plasma levels in SCA subjects who presented with acute painful episodes.
MATERIALS AND METHODS
PBMC were isolated from the blood of SCA subjects and normal healthy controls. RNA isolated from PBMC was used for real time gene expression of TL1A/DR3/DcR3. Gene expression was compared in subgroups within SCA subjects with co-inherited fetal hemoglobin (HbF) or alpha-globin gene deletions. Plasma prepared from blood was used for determination of TL1A/DR3/DcR3 proteins by ELISA assays.
RESULTS
In the PBMC of SCA subjects, expression of TL1A and DcR3 is elevated, while DR3 expression is lowered in comparison to normal control PBMC. In SCA subjects with HbF > 10%, TL1A/DcR3 expression is lower, while HbF < 10% is associated with increased TL1A/DcR3 expression. Moreover, subjects with HbF > 10% appear to have significantly fewer pain episodes in comparison to those with HbF < 10%. Deletion of alpha-globin genes appears to have no significant effect on TL1A/DR3/DcR3 expression. Circulating levels of TL1A, DR3 and DcR3 in plasma were significantly elevated in SCA subjects.
CONCLUSIONS
Elevated TL1A and DcR3 expression in PBMC of SCA subjects during painful vasoocclusive crisis, suggest an altered TL1A expression may contribute to the pathophysiology of vasoocclusive crisis in SCA. HbF > 10% appears to moderate TL1A elevation, while HbF < 10% exacerbates TL1A/DcR3 responses. Furthermore, subjects with HbF > 10% have significantly lower pain episodes reported as compared to subjects with HbF < 10%.
背景
镰状细胞贫血（SCA）是一种具有重要炎症成分的疾病，血管阻塞是其病理生理学的主要原因。促炎细胞因子在炎症过程中起着重要的调节作用。我们研究了 SCA 患者在出现急性疼痛发作时外周血单核细胞（PBMC）中 TL1A/DR3/DcR3 细胞因子信号通路的表达及其相应的血浆水平。
材料和方法
从 SCA 患者和正常健康对照者的血液中分离 PBMC。从 PBMC 中提取的 RNA 用于实时基因表达 TL1A/DR3/DcR3。在 SCA 患者中，根据共遗传胎儿血红蛋白（HbF）或α-珠蛋白基因缺失情况对亚组进行比较。从血液中制备的血浆用于通过 ELISA 测定 TL1A/DR3/DcR3 蛋白。
结果
在 SCA 患者的 PBMC 中，与正常对照 PBMC 相比，TL1A 和 DcR3 的表达升高，而 DR3 的表达降低。在 HbF>10%的 SCA 患者中，TL1A/DcR3 的表达较低，而 HbF<10%与 TL1A/DcR3 表达增加有关。此外，与 HbF<10%的患者相比，HbF>10%的患者似乎疼痛发作次数明显减少。α-珠蛋白基因缺失似乎对 TL1A/DR3/DcR3 表达没有显著影响。SCA 患者血浆中 TL1A、DR3 和 DcR3 的循环水平显著升高。
结论
在 SCA 患者发生疼痛性血管阻塞危象时，PBMC 中 TL1A 和 DcR3 的表达升高，提示 TL1A 表达的改变可能导致 SCA 血管阻塞危象的病理生理学改变。HbF>10%似乎可以调节 TL1A 的升高，而 HbF<10%则加剧 TL1A/DcR3 的反应。此外，与 HbF<10%的患者相比，HbF>10%的患者报告的疼痛发作明显减少。
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