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Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways

  
@article{APS7932,
	author = {Zhe Meng and Chao Yan and Qian Deng and Deng-feng Gao and Xiao-lin Niu},
	title = {Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways},
	journal = {Acta Pharmacologica Sinica},
	volume = {34},
	number = {7},
	year = {2016},
	keywords = {},
	abstract = {Zhe MENG1, Chao YAN1, Qian DENG2, Deng-feng GAO1, *, Xiao-lin NIU1, *
1Department of Cardiology, The Second Affiliated Hospital, Xi-an Jiaotong University School of Medicine, Xi’an 710004, China; 2Department of Urology, The Second Affiliated Hospital, Xi-an Jiaotong University School of Medicine, Xi’an 710004, China
 
Aim: To investigate whether curcumin (Cur) suppressed lipopolysaccharide (LPS)-induced inflammation in vascular smooth muscle cells (VSMCs) of rats, and to determine its molecular mechanisms.  
Methods: Primary rat VSMCs were treated with LPS (1 μg/L) and Cur (5, 10, or 30 μmol/L) for 24 h.  The levels of MCP-1, TNF-α, and iNOS were measured using ELISA and real-time RT-PCR.  NO level was analyzed with the Griess reaction.  Western-blotting was used to detect the activation of TLR4, MAPKs, IκBα, NF-κB p65, and the p47phox subunit of NADPH oxidase in the cells.

Results: Treatment of VSMCs with LPS dramatically increased expression of inflammatory cytokines MCP-1 and TNF-α, expression of TLR4 and iNOS, and NO production.  LPS also significantly increased phosphorylation of IκBα, nuclear translocation of NF-κB (p65) and phosphorylation of MAPKs in VSMCs.  Furthermore, LPS significantly increased production of intracellular ROS, and decreased expression of p47phox subunit of NADPH oxidase.  Pretreatment with Cur concentration-dependently attenuated all the aberrant changes in LPS-treated VSMCs.  The LPS-induced overexpression of MCP-1 and TNF-α, and NO production were attenuated by pretreatment with the ERK inhibitor PD98059, the p38 MAPK inhibitor SB203580, the NF-κB inhibitor PDTC or anti-TLR4 antibody, but not with the JNK inhibitor SP600125.

Conclusion: Cur suppresses LPS-induced overexpression of inflammatory mediators in VSMCs in vitro via inhibiting the TLR4-MAPK/NF-κB pathways, partly due to block of NADPH-mediated intracellular ROS production.

 
Keywords: curcumin; vascular smooth muscle cell; atherosclerosis; inflammation; lipopolysaccharide; monocyte chemotactic protein-1 (MCP-1); TNF-α; Toll-like receptor 4 (TLR4); mitogen-activated protein kinases (MAPK); NF-κB; reactive oxygen species (ROS); NADPH
 
This study was supported by the National Natural Science Foundation of China [NSFC 81070219 to Xiao-lin NIU and NSFC 30900617 to Deng-feng GAO].
* To whom correspondence should be addressed.
E-mail niuxl@mail.xjtu.edu.cn (Xiao-lin NIU); xniuxl@mail.xjtu.edu.cn (Deng-feng GAO)
Received 2012-11-02    Accepted 2013-02-27},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/7932}
}