title: Curcumin inhibits LPS-induced CCL2 expression via JNK pathway in C6 rat astrocytoma cells.
abstract: The important role of neuroinflammation in many chronic and acute pathological conditions of the central nervous system is widely recognized. Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. This study investigated the inhibitory effect of curcumin on lipopolysacharide (LPS)-induced chemokine CCL2 (or monocyte chemoattractant protein-1, MCP-1) production and whether the effect is mediated by mitogen-activated protein kinases (MAPKs) in the rat astrocytoma cell C6. We observed that LPS (1 μg/ml) induced the upregulation of CCL2 mRNA and protein in C6. Treatment with curcumin (2.5, 10, and 25 μM) decreased the expression of CCL2 mRNA and protein in a dose-dependent manner under treatment with LPS. Additionally, the c-jun N-terminal kinase (JNK) inhibitor (SP600125) dose-dependently inhibited LPS-induced CCL2 upregulation, whereas the MAPK kinase (MEK) inhibitor (PD98059) only had a mild effect and the p38 MAPK inhibitor (SB203580) had no effect. Finally, western blot showed that LPS induced rapid JNK activation and curcumin reduced LPS-induced phosphoJNK (pJNK) expression at 30 min after LPS stimulation. These data suggest that the anti-neuroinflammatory effect of curcumin relates to the downregulation of CCL2 expression through the JNK pathway in astrocytoma cells, which indicates a possible benefit from the use of curcumin in the treatment of neuroinflammation-associated disorders.
authors.affiliation: Department of Anatomy & Cytoneurobiology Unit, Medical College, Soochow University, Suzhou Industrial Park, Suzhou, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Lin-Xia
authors.initials: LX
authors.lastname: Zhao
authors.forename: De-Li
authors.initials: DL
authors.lastname: Cao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong-Jing
authors.initials: YJ
authors.lastname: Gao
authors.forename: Chunlin
authors.initials: C
authors.lastname: Xia
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin