p38 Mitogen-Activated Protein Kinase Is Involved in Interleukin-6 Secretion from Human Ligamentum Flavum-Derived Cells Stimulated by Tumor Necrosis Factor-α.
p38 Mitogen-Activated Protein Kinase Is Involved in Interleukin-6 Secretion from Human Ligamentum Flavum-Derived Cells Stimulated by Tumor Necrosis Factor-α.
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DOI：
10.31616/asj.2020.0425
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发表时间：
2021-12
影响因子：
2.3
通讯作者：
Murakami H
中科院分区：
文献类型：
--
作者：
Yagi K;Goto Y;Kato K;Suzuki N;Kondo A;Waseda Y;Mizutani J;Kawaguchi Y;Joyo Y;Waguri-Nagaya Y;Murakami H
从手术样本中获得人类韧带黄素来源细胞（hfc），用于基础实验研究。我们试图评估人类黄韧带细胞的炎症反应，以研究黄韧带发生的肥厚变化。腰椎管狭窄症（LSS）是一种常见于老年人的疾病。随着时间的推移，LSS患者的数量不断增加，但LSS的病理机制仍未完全阐明。LSS的临床特征之一是黄韧带肥大，导致腰椎管狭窄。一些报道表明，黄韧带肥大与炎症和纤维化有关；同时，p38丝裂原活化蛋白（MAP）激酶参与了人黄韧带细胞的肥大。氢氟碳化物是从接受手术的LSS患者中获得的。hfc受到肿瘤坏死因子-α (TNF-α)和p38 MAP激酶抑制剂SB203580的刺激。western blotting分析p38 MAP激酶磷酸化水平。酶联免疫法检测条件培养基中白细胞介素-6 （IL-6）的浓度，实时聚合酶链反应检测IL-6信使RNA的表达水平。TNF-α以时间依赖性的方式诱导p38 MAP激酶磷酸化，该磷酸化被p38 MAP激酶抑制剂SB203580抑制。TNF-α也以时间和剂量依赖的方式刺激IL-6释放。SB203580本身不刺激氢氟碳化物分泌IL-6；然而，它能显著抑制氢氟碳化物中TNF-α刺激的IL-6释放程度。这是首次报道TNF-α通过p38 MAP激酶刺激HFCs中IL-6的基因表达和蛋白分泌。组织肥大和炎症之间的关联表明p38 MAP激酶炎症途径可能是LSS的治疗分子靶点。
Human ligamentum flavum–derived cells (HFCs) were obtained from surgical samples for a basic experimental study. We sought to evaluate the inflammatory response of human ligamentum flavum cells to investigate hypertrophic changes occurring in the ligamentum flavum. Lumbar spinal stenosis (LSS) is a disease commonly observed in the elderly. The number of patients with LSS has increased over time, yet the pathomechanisms of LSS still have not been fully elucidated. One of the clinical features of LSS is hypertrophy of the ligamentum flavum, which results in narrowing of the lumbar spinal canal. Some reports have suggested that ligamentum flavum hypertrophy is associated with inflammation and fibrosis; meanwhile, the p38 mitogen-activated protein (MAP) kinase is involved in the hypertrophy of human ligamentum flavum cells. HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.
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影响因子：
3
作者：
Chen, Yi-Te;Wei, Jyh-Ding;Hung, Shih-Chieh
通讯作者：
Hung, Shih-Chieh
影响因子：
3
作者：
Sairyo, Koichi;Biyani, Ashok;Mohan, Suneeth E.
通讯作者：
Mohan, Suneeth E.
影响因子：
1.7
作者：
Fujita, Nobuyuki;Sakurai, Aiko;Watanabe, Kota
通讯作者：
Watanabe, Kota
影响因子：
3
作者：
Markman, John D.;Gewandter, Jennifer S.;Dworkin, Robert H.
通讯作者：
Dworkin, Robert H.
影响因子：
2.8
作者：
Tuomainen, I.;Aalto, T.;Airaksinen, O.
通讯作者：
Airaksinen, O.