title: Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide-induced astrocyte reactivation in vitro.
abstract: Curcumin has been proposed for treatment of various neuroinflammatory and neurodegenerative conditions, including post-traumatic inflammation during acute spinal cord injury (SCI). In this study, we examined whether curcumin anti-inflammation involves regulation of astrocyte reactivation, with special focus on the injury-induced RANTES (regulated on expression normal T-cell expressed and secreted) from astrocytes in acute SCI. Male Sprague-Dawley (SD) rats were subjected to impact injury of the spinal cord followed by treatment with curcumin (40 mg/kg i.p.). RANTES and inducible nitric oxide synthase expression as well as RANTES-positive astrocytes were all induced by injury accompanied by the elevation of lipid peroxidation, and attenuated by the curcumin treatment. In primary cultured rat astrocytes challenged with lipopolysaccharide (LPS) to mimic astrocyte reactivation following SCI, LPS induces robust increase of RANTES expression and the effect was also reduced by 1 μM curcumin treatment. Furthermore, cortical neurons cultured with astrocyte conditioned medium (ACM) conditioned with both LPS and curcumin (LPS-curcumin/ACM), which characteristically exhibited decreased RANTES expression when compared with ACM from astrocytes treated with LPS alone (LPS/ACM), showed higher level of cell viability and lower level of cell death as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity assay and lactate dehydrogenase release assay, respectively. Knockdown of RANTES expression by siRNA (siRANTES) shows reduced RANTES expression and release from LPS-reactivated astrocytes, and ACM obtained from this condition (LPS-siRANTES/ACM) becomes less cytotoxic as compared with the LPS-ACM. Therefore, curcumin reduction of robust RANTES production in reactivated astrocytes both in vitro and in vivo may contribute to its neuroprotection and potential application in SCI.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Muh-Shi
authors.initials: MS
authors.lastname: Lin
authors.forename: Yu-Yo
authors.initials: YY
authors.lastname: Sun
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Hung
authors.forename: Chiu-Yun
authors.initials: CY
authors.lastname: Chang
authors.forename: Feng-Shiun
authors.initials: FS
authors.lastname: Shie
authors.forename: Shin-Han
authors.initials: SH
authors.lastname: Tsai
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Lin
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Hung
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism*; D018920:Coculture Techniques; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018946:Chemokine CCL5; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D003474:Curcumin