非甾体抗炎药双氯芬酸、吲哚美辛和美洛昔康可显著上调人内皮细胞中由X射线照射诱导的细胞间黏附分子-1（ICAM-1）和环氧化酶-2（COX-2）的表达。

NSAIDs diclofenac, indomethacin, and meloxicam highly upregulate expression of ICAM-1 and COX-2 induced by X-irradiation in human endothelial cells.

作者信息

Uehara Yoshihiko, Murata Yasuhiko, Shiga Soichiro, Hosoi Yoshio

机构信息

Department of Radiation Biology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken 980-8575, Japan.

出版信息

Biochem Biophys Res Commun. 2016 Oct 28;479(4):847-852. doi: 10.1016/j.bbrc.2016.09.120. Epub 2016 Sep 28.

DOI:10.1016/j.bbrc.2016.09.120

PMID:27687548

Abstract

BACKGROUND

It is well known that radiation exposure to the heart and the use of non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of myocardial infarction (MI). Some NSAIDs are also known to act synergistically with ionizing radiation and have radio-sensitizing effects in radiotherapy. These evidences suggest that NSAIDs may affect the risk of MI after radiation exposure to the heart. In the present study, we investigated effects of NSAIDs on radiation-induced expression of cell adhesion molecules and COX-2, which are associated with inflammation and an increased risk of MI, in human endothelial cells.

METHODS

Effects of NSAIDs on radiation-induced expression of ICAM-1, VCAM-1, E-selectin, and COX-2 were investigated in human umbilical vein endothelial cells (HUVECs). As NSAIDs, diclofenac, etodolac, indomethacin, ketoprofen, meloxicam, and rofecoxib were used.

RESULTS

Irradiation with 10 Gy increased expression of ICAM-1 and COX-2, but it did not affect expression of VCAM-1 or E-selectin. All the NSAIDs upregulated radiation-induced expression of ICAM-1 and COX-2. The extent of upregulation varied depending on the types of NSAIDs. Indomethacin, diclofenac, and meloxicam highly upregulated radiation-induced expression of ICAM-1 and COX-2. The extent of upregulation was not related to the degree of COX-2 selectivity. An NF-κB inhibitor BAY 11-7082 suppressed radiation-induced expression of ICAM-1, but it did not suppress upregulated expression of ICAM-1 or COX-2 by combination treatment with X-irradiation and meloxicam, suggesting the existence of NF-κB-independent pathways for ICAM-1 and COX-2 induction.

CONCLUSION

Indomethacin, diclofenac, and meloxicam highly upregulated radiation-induced expression of ICAM-1 and COX-2 in HUVECs, which suggests that use of these NSAIDs may increase the effects of ionizing radiation and affect the risk of MI after radiation exposure to the heart.

摘要

背景

众所周知，心脏受到辐射以及使用非甾体抗炎药（NSAIDs）会增加心肌梗死（MI）的风险。一些NSAIDs还已知与电离辐射协同作用，并在放射治疗中具有放射增敏作用。这些证据表明，NSAIDs可能会影响心脏受到辐射后发生MI的风险。在本研究中，我们调查了NSAIDs对人内皮细胞中与炎症和MI风险增加相关的细胞粘附分子和COX-2辐射诱导表达的影响。

方法

在人脐静脉内皮细胞（HUVECs）中研究了NSAIDs对辐射诱导的ICAM-1、VCAM-1、E-选择素和COX-2表达的影响。使用双氯芬酸、依托度酸、吲哚美辛、酮洛芬、美洛昔康和罗非昔布作为NSAIDs。

结果

10 Gy的照射增加了ICAM-1和COX-2的表达，但未影响VCAM-1或E-选择素的表达。所有NSAIDs均上调了辐射诱导的ICAM-1和COX-2的表达。上调程度因NSAIDs类型而异。吲哚美辛、双氯芬酸和美洛昔康高度上调了辐射诱导的ICAM-1和COX-2的表达。上调程度与COX-2选择性程度无关。NF-κB抑制剂BAY 11-7082抑制了辐射诱导的ICAM-1表达，但未抑制X射线照射与美洛昔康联合治疗引起的ICAM-1或COX-2上调表达，提示存在ICAM-1和COX-2诱导的NF-κB非依赖途径。