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

• Published in: Acta pharmacologica Sinica 2013-07, Vol.34 (7), p.901-911
• Main Authors: Meng, Zhe, Yan, Chao, Deng, Qian, Gao, Deng-feng, Niu, Xiao-lin
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Curcumin - pharmacology; Immunology; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; Internal Medicine; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - chemistry; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Medical Microbiology; Muscle, Smooth, Vascular - chemistry; Muscle, Smooth, Vascular - immunology; Muscle, Smooth, Vascular - metabolism; NF-kappa B - chemistry; NF-kappa B - physiology; Original; original-article; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - chemistry; Reactive Oxygen Species - metabolism; Toll-Like Receptor 4 - physiology; Vaccine
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2013.24

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 p47 phox 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 p47 phox 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.