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ȣ - 490034 4 |
| Curcumin Protects Endothelial Cells from Pro-Inflammatory Response; via Inhibition of Nuclear Factor-κB, p38, c-Jun N-Terminal Kinase, and Signal Transducer and Activator of Transcription-3 |
| 전남대학교 병원 순환기내과 |
| 김용숙, 안영근, 홍문화, 주수연, 김계훈, 손일석, 홍영준, 박형욱, 김주한, 김원, 정명호, 조정관, 박종춘, 강정채 |
Background: Curcumin, a yellow pigment of tumeric in curry, is reported to interfere with nuclear factor (NF)-κB. This study was designed to investigate the underlying pathway of anti-inflammatory action of curcumin on endothelial cells. Methods: Human umbilical vein endothelial cell (HUVEC) was stimulated with tumor necrosis factor (TNF)-α (10 ng/mL). NF-κB p65 activation was determined by immunocytochemistry. Intracellular level of reactive oxygen species (ROS) was measured by using fluorescent dye and the extent of inflammation was determined by U937 monocyte adhesion assay. The expressions of vascular adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8 were determined at transcriptional and translational levels. The activation of c-Jun N-terminal kinase (JNK), p38, and signal transducer and activator of transcription (STAT)-3 were examined by immunoblot. To confirm the anti-NF-κB effect of curcumin, BAY 11-7082, a selective inhibitor of NF-κB, was used to compare with the effects of curcumin. Results: Immunocytochemical study revealed nuclear translocation of NF-κB p65 by TNF-α was inhibited significantly by curcumin (10 μM) in HUVEC. Curcumin suppressed intracellular ROS level (62.7% decreased, p=0.008) and U937 monocyte adhesion (100% decreased, p=0.001) in TNF-α-stimulated HUVEC. Phosphorylations of JNK, p38, and STAT-3 in TNF-α stimulated HUVEC were also inhibited by curcumin pretreatment. The expressions of VCAM-1, ICAM-1, MCP-1, and IL-8 were attenuated by curcumin at both transcription and translation level. On the other hand, BAY 11-7082 reduced the expressions of VCAM-1, ICAM-1, MCP-1, and IL-8 at mRNA and protein levels, whereas, it had no effects on ROS level and phosphorylations of JNK and p38. Conclusions: This is the first report that curcumin modulates STAT-3 activity in human endothelium. Curcumin inhibited the NF-κB activation to control the pro-inflammatory response, with additional inhibition of ROS generation, JNK, and p38 in endothelial cells. These results suggested that curcumin-diet may be beneficial to the patients who is under vascular wall inflammation.
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