Endogenous TGF‐β activity limits TSLP expression in the intervertebral disc tissue by suppressing NF‐κB activation
Endogenous TGF‐β activity limits TSLP expression in the intervertebral disc tissue by suppressing NF‐κB activation
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DOI：
10.1002/jor.22337
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发表时间：
2013-07
影响因子：
2.8
通讯作者：
Yong-Ming Zhu;Tetsuro Ohba;Takashi Ando;Koji Fujita;Kensuke Koyama;Yuki Nakamura;R. Katoh,;H. Haro;A. Nakao
中科院分区：
文献类型：
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作者：
Yong-Ming Zhu;Tetsuro Ohba;Takashi Ando;Koji Fujita;Kensuke Koyama;Yuki Nakamura;R. Katoh,;H. Haro;A. Nakao
胸腺基质淋巴细胞生成素 (TSLP) 是一种 IL-7 样细胞因子，在椎间盘突出 (HD) 组织中高表达，可能作为启动巨噬细胞招募到组织中和 HD 自然吸收的关键分子。然而，目前尚不清楚 TSLP 表达在椎间盘中是如何调节的。这项研究表明，HD 组织样本中 TSLP 和磷酸化 NF-κB 的表达与磷酸化 Smad2/3（活跃 TGF-β 信号传导的指标）的表达呈负相关，在后腰椎融合样本中反之亦然。药理学阻断内源性 TGF-β 活性可诱导小鼠椎间盘组织培养物中 TSLP 的表达，而 TSLP 表达可被 NF-κB 抑制剂抑制。此外，在稳定状态下的小鼠椎间盘组织中检测到 Smad2/3 的磷酸化。总的来说，这些结果表明内源性 TGF-β 活性通过抑制 NF-κB 激活来限制稳定状态下椎间盘组织中的 TSLP 表达。研究结果揭示了椎间盘组织中诱导 TSLP 表达的调节机制，并提示 TGF-β 在维持椎间盘组织稳态中的新作用。 © 2013 骨科研究协会，Wiley periodicals, Inc. 出版。J Orthop Res 31:1144–1149, 2013
Thymic stromal lymphopoietin (TSLP), an IL‐7‐like cytokine, is highly expressed in herniated disc (HD) tissue and may act as a key molecule for the initiation of macrophage recruitment into the tissue and natural resorption of HD. However, it remains unclear how TSLP expression is regulated in the intervertebral discs. This study showed that expression of TSLP and phosphorylated NF‐κB in HD tissue samples was inversely correlated with expression of phosphorylated Smad2/3 (an indicator of active TGF‐β signaling) and vice versa in posterior lumbar spinal fusion samples. The pharmacological blockades of endogenous TGF‐β activity induced TSLP expression in mouse intervertebral disc tissue culture, which was inhibited by NF‐κB inhibitors. Additionally, phosphorylation of Smad2/3 was constitutively detected in mouse intervertebral disc tissue in the steady states. Collectively, these results suggest that endogenous TGF‐β activity limits TSLP expression in intervertebral disc tissue in the steady states by suppressing NF‐κB activation. The findings reveal a regulatory mechanism how TSLP expression is induced in the intervertebral disc tissue and suggest a novel role of TGF‐β in maintaining the homeostasis of intervertebral disc tissue. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1144–1149, 2013