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    
Abstract/OtherAbstract:
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.
Authors:
Sebastien Boridy; Ghareb M Soliman; Dusica Maysinger
Related Documents :
22918439 - Conservation of caspase substrates across metazoans suggests hierarchical importance of...
22884959 - Central administration of murine interferon-α induces depressive-like behavioral, brain...
22469979 - Smac mimetic sensitizes glioblastoma cells to temozolomide-induced apoptosis in a rip1-...
22748649 - Immunotherapy for glioma: promises and challenges.
22653339 - C/ebp homologous protein contributes to cytokine-induced pro-inflammatory responses and...
19125209 - Cascading effects of stressors and inflammatory immune system activation: implications ...
24065159 - Towards the small and the beautiful: a small dibromotyrosine derivative from pseudocera...
20800309 - Malignant but not naïve hepatocytes of human and rodent origin are killed by tnf after ...
12844389 - The oral immunogenicity of bioprotein, a bacterial single-cell protein, is affected by ...
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:  -    
Affiliation:
Department of Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC, H3G 1Y6, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round wi...
Next Document:  Nanowires precisely grown on the ends of microwire electrodes permit the recording of intracellular ...