The Novel NF-κB Inhibitor, MTI-II Peptide Anti-Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast-Like Cells
The Novel NF-κB Inhibitor, MTI-II Peptide Anti-Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast-Like Cells
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新型 NF-κB 抑制剂 MTI-II 肽抗炎药可抑制成牙本质细胞样细胞的炎症反应
DOI：
10.1002/jcb.25548
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发表时间：
2016
期刊：
影响因子：
4
通讯作者：
Kitamura C.
中科院分区：
文献类型：
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作者：
Nakayama K;Hirata-Tsuchiya S;Okamoto K;Morotomi T;Jimi E;Kitamura C.
炎症的调节对牙髓伤口的愈合很重要，包括成牙本质细胞样细胞的保护性反应。然而，直接调节牙髓炎症的方法尚未被描述。炎症反应是由转录因子核因子-κB(NF-κB)介导的，它激活包括肿瘤坏死因子-α在内的炎性细胞因子。大分子易位抑制因子II(MTI-II)是糖皮质激素结合的糖皮质激素受体转录活性的增强剂。最近，从MTI-II的结构中筛选出一种抑制核因子-κB反式激活的多肽抗炎药。在这里，我们研究了MTI-II和MPAID对成牙本质细胞样细胞炎症反应的影响。肿瘤坏死因子-α抑制成牙本质细胞/成骨分化标志物碱性磷酸酶的活性，并诱导KN-3细胞的转录活性。KN-3细胞是大鼠切牙乳头细胞来源的成牙本质细胞样细胞，其活性不受影响。外源性表达MTI-II可抑制肿瘤坏死因子-κB或p65(核因子-α的主要亚基)诱导的转录活性，但不能抑制I-κB的降解和p65的核转位，提示MTI-II通过调节p65与κ结合的时间而抑制核转录活性。MPAID还可抑制肿瘤坏死因子α诱导的NF-κB转录活性、IL-6和IL-8mRNA的表达以及IL-6的产生。此外，MPAID可恢复肿瘤坏死因子-α对碱性磷酸酶活性的抑制作用。提示MPAID可能具有调节牙髓炎症反应、维持牙髓保护性反应的作用。J.细胞。生物化学。117：2552-2558,2016。©2016 Wiley期刊，Inc.
Regulation of inflammation is important for pulp wound healing, including protective responses by odontoblast‐like cells. However, methods for directly regulating pulp inflammation have not yet been described. The inflammatory response is mediated by a transcription factor, nuclear factor‐κB (NF‐κB), which activates inflammatory cytokines including tumor necrosis factor (TNF)‐α. Macromolecular translocation inhibitor II (MTI‐II) was previously demonstrated as an enhancer of the transcriptional activity of glucocorticoid‐bound glucocorticoid receptor. Recently, a MTI‐II peptide anti‐inflammatory drug (MPAID) was bioengineered from the structure of MTI‐II as an inhibitor of NF‐κB transactivation. Here, we examined the effects of MTI‐II and MPAID on the inflammatory responses of odontoblast‐like cells. TNF‐α inhibited alkaline phosphatase (ALP) activity, a marker of odontoblast/osteogenic differentiation, and induced NF‐κB transcriptional activity in KN‐3 cells, which are odontoblast‐like cells derived from dental papilla cells of rat incisors, without affecting their viability. Exogenous expression of MTI‐II suppressed the NF‐κB transcriptional activity induced by TNF‐α or overexpression of p65 (a main subunit of NF‐κB) in the cells, whereas it failed to inhibit degradation of IκBα and nuclear translocation of p65 after TNF‐α treatment, suggesting that MTI‐II inhibits NF‐κB transcriptional activity by modulating the duration of DNA binding by p65. MPAID also inhibited TNF‐α‐induced NF‐κB transcriptional activity, the mRNA expression of IL‐6 and IL‐8, and IL‐6 production. Furthermore, pretreatment of the cells with MPAID restored the inhibitory effect of TNF‐α on ALP activity. These results suggest that MPAID may be able to regulate the inflammatory response and maintain a protective response of dental pulp. J. Cell. Biochem. 117: 2552–2558, 2016. © 2016 Wiley Periodicals, Inc.