Document Detail

Modulation of inflammatory signaling and cytokine release from microglia by celastrol incorporated into dendrimer nanocarriers.
MedLine Citation:
PMID:  22475649     Owner:  NLM     Status:  Publisher    
Aims: This study investigates the capacity of a potent anti-inflammatory nanomedicine, celastrol, incorporated into poly(amidoamine) dendrimers, to inhibit endotoxin-mediated signaling in microglia. Materials & methods: Celastrol was incorporated into amino (Cel/G4-NH(2)) and hydroxyl (Cel/G4-OH) terminus poly(amidoamine) (G4) dendrimers. Cell viability, release of nitric oxide, IL-6, TNF-α and activation of MAPK (e.g., p38 and JNK) and NF-κB were assessed in endotoxin (i.e., lipopolysaccharide) -stimulated microglial cells. Results: G4-OH and G4-NH(2) increased celastrol aqueous solubility by seven- and 12-fold, respectively. G4-OH and Cel/G4-OH suppressed lipopolysaccharide-mediated release of proinflammatory mediators, such as nitric oxide and IL-6, but not TNF-α, without reducing microglial cell viability, while Cel/G4-NH(2) potentiated cytotoxicity and cytokine release. Blockade of proinflammatory signaling was accompanied by attenuation of p38 MAPK activation. Conclusion: This study supports the potential use of poly(amidoamine) dendrimers for effective anti-inflammatory therapy in the chronically inflamed CNS. Original submitted 22 July 2011; Revised submitted 8 December 2011.
Sebastien Boridy; Ghareb M Soliman; Dusica Maysinger
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-4
Journal Detail:
Title:  Nanomedicine (London, England)     Volume:  -     ISSN:  1748-6963     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101278111     Medline TA:  Nanomedicine (Lond)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC, H3G 1Y6, Canada.
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