Curcumin Attenuates Nuclear Factor-κB, c-Jun N-Terminal Kinase and p38 in Tumor Necrosis Factor-α-Stimulated Endothelial Cells

다국어 초록 (Multilingual Abstract)

Background and Objectives：Curcumin, a yellow pigment of turmeric in curry, has been reported to interferewith nuclear factor (NF)-κB. This study was designed to investigate the underlying pathway of the anti-inflammationeffect of curcumin on endothelial cells. Materials and Methods：Human umbilical vein endothelial cells(HUVECs) were stimulated with tumor necrosis factor (TNF)-α (10 ng/mL). The levels of intracellular reactiveoxygen species (ROS) were examined using a fluorescent dye DCFH-DA, and the adhesion of U-937 monocytesto the HUVECs was then examined. Nuclear factor kappa B (NF-κB) activation was determined by the NF-κBp65 translocation to the nucleus via immunocytochemistry. The expression of the NF-κB dependent pro-inflammatorymolecules were measured by RT-PCR and ELISA. The phosphorylations of c-Jun N-terminal proteinkinase (JNK), p38 and STAT-3 (signal transducer and activator of transcription-3) were measured by Westernblotting. Results：Curcumin blocked the activation of NF-κB by TNF-α, and it also reduced the ROS, monocyteadhesion and the phosphorylation of JNK, p38 and STAT-3 in the TNF-α-stimulated HUVECs. The expressionof intracellular cell adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, and interleukin(IL)-8 were attenuated by curcumin at both the transcription and translation levels. Conclusion：We suggest thatcurcumin could contribute to protection against the adverse vascular effects of the pro-inflammatory responsethrough the modulation of NF-κB, JNK, p38 and STAT-3, and this is in addition to its antioxidant effect inendothelial cells. (Korean Circulation J 2006;36:482-489)

참고문헌 (Reference)

1 "The functional role ofthe JAK-STAT pathway in post-infarction remodeling" 57 : 129-138, 2003

2 "The anti-inflammatorycompound curcumin inhibits Neisseria gonorrhoeaeinducedNF-kappaB signaling,release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection" 386 : 481-490, 2005

3 "Suppression of protein kinase C and nuclear oncogeneexpression as possible action mechanisms of cancer chemopreventionby Curcumin" 27 : 683-692, 2004

4 "Stress-responsive protein kinases in redox-regulated apoptosis signaling" 7 : 472-481, 2005

5 "Stress signaling pathways that modulatecardiac myocyte apoptosis" 38 : 47-62, 2005

6 "Signal transduction by tumor necrosis factorand its relatives" 11 : 372-377, 2001

7 "Role of STAT3 and PI 3-kinase/Akt in mediating the survival actions of cytokines on sensoryneurons" 18 : 270-282, 2001

8 "Principles of interleukin(IL)-6-type cytokinesignalling and its regulation" 374 : 1-20, 2003

9 "Nuclear factor-kappaB:a pivotal transcriptionfactor in chronic inflammatory diseases" 336 : 1066-1071, 1997

10 "N-acetylcysteine inhibited nuclear factor-kappaBexpression and the intimal hyperplasia in rat carotid arterial injury" 23 : 731-738, 2001

11 "JNK potentiates TNF-stimulated necrosis by increasing the productionof cytotoxic reactive oxygen species" 18 : 2905-2915, 2004

12 "In vivo cardiac gene transferof dominant negative IKK-β reduces myocardial inflammation,apoptosis,and infarction after ischemia-reperfusion injury" 35 : 206-214, 2005

13 "How cells respond to interferons" 67 : 227-264, 1998

14 "Expression of tumor necrosis factor receptor superfamily in carotidatheroma" 30 : 1563-1573, 2000

15 "Differentialanti-inflammatory and anti-oxidative effects of dexamethasoneand N-acetylcysteine in endotoxin-induced lung inflammation" 122 : 249-256, 2000

16 "Curcumin,an anti-tumour promoter andanti-inflammatory agent,inhibits induction of nitric oxide synthasein activated macrophages" 206 : 533-540, 1995

17 "Curcumin(diferuloylmethane)inhibits constitutive and IL-6-inducible STAT3 phosphorylationin human multiple myeloma cells" 171 : 3863-3871, 2003

18 "Curcumin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression by inhibitingactivator protein 1 and nuclear factor kappab bindings in BV2microglial cells" 94 : 325-328, 2004

19 "Curcumin suppresses Januskinase-STAT inflammatory signaling through activation of Srchomology 2 domain-containing tyrosine phosphatase 2 in brainmicroglia" 171 : 6072-6079, 2003

20 "Curcumin inhibits experimental allergicencephalomyelitis by blocking IL-12 signaling through Januskinase-STAT pathway in T lymphocytes" 168 : 6506-6513, 2002

21 "Curcumin inhibits NF-kappaB activation and reduces the severityof experimental steatohepatitis in mice" 41 : 926-934, 2004

22 "Carvedilol inhibits expressionsof vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant-1, and interleukin-8 via NF-κB inhibition in human endothelial cells" 35 : 576-582, 2005

23 "Atherosclerosis" 407 : 233-241, 2000

24 "Atheroclerosis:an inflammatory disease" 340 : 115-126, 1999

25 "Activation of JAK/STATpathway transduces cytoprotective signal in rat acute myocardialinfarction" 47 : 797-805, 2000