TY - JOUR
T1 - NSAIDs diclofenac, indomethacin, and meloxicam highly upregulate expression of ICAM-1 and COX-2 induced by X-irradiation in human endothelial cells
AU - Uehara, Yoshihiko
AU - Murata, Yasuhiko
AU - Shiga, Soichiro
AU - Hosoi, Yoshio
N1 - Funding Information:
This work was supported by Grant-in Aid for Challenging Exploratory Research, Grant Number 26670547 from the Ministry of Education, Culture, Sports, Science and Technology of Japan .
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/28
Y1 - 2016/10/28
N2 - 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.
AB - 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.
KW - COX inhibitor
KW - COX-2
KW - Endothelial cells
KW - ICAM-1
KW - NSAIDs
KW - Radiation
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U2 - 10.1016/j.bbrc.2016.09.120
DO - 10.1016/j.bbrc.2016.09.120
M3 - Article
C2 - 27687548
AN - SCOPUS:84991669684
SN - 0006-291X
VL - 479
SP - 847
EP - 852
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -