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E-GEOD-24579 - Potentiation of glucocorticoid signaling by chloroquine via inhibition of lysosomes

Status
Released on 18 January 2012, last updated on 26 June 2012
Organism
Homo sapiens
Samples (4)
Array (1)
Protocols (6)
Description
Anti-malaria drug chloroquine has been used as an anti-inflammatory agent for treating systemic lupus erythematosus and rheumatoid arthritis, without clear mechanism of action. Here we report that chloroquine potently inhibits the expression of proinflammatory cytokines through transrepression of glucocorticoid receptor (GR). Instead of direct binding to GR, chloroquine synergistically activates glucocorticoid signaling via inhibition of lysosomal functions. In mouse collagen induced arthritis model, chloroquine synergizes the therapeutic effects of glucocorticoid. Lysosomal inhibition by bafilomycin A1, an inhibitor of V-type ATPase, or by knockdown of transcription factor EB (TFEB), a master activator of lysosomal biogenesis, mimics the effects of chloroquine. These results reveal an unexpected regulation of glucocorticoid signaling by lysosomes and provide a mechanistic basis for treating inflammation and autoimmune diseases by combination of glucocorticoids and lysosomal inhibitors. Macrophage THP-1 cells treated with LPS, chloroquine and dexamethasone.
Experiment type
transcription profiling by array 
Contacts
Citation
Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. He Y, Xu Y, Zhang C, Gao X, Dykema KJ, Martin KR, Ke J, Hudson EA, Khoo SK, Resau JH, Alberts AS, MacKeigan JP, Furge KA, Xu HE. , PMID:21730326
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-24579.idf.txt
Sample and data relationshipE-GEOD-24579.sdrf.txt
Raw data (1)E-GEOD-24579.raw.1.zip
Processed data (1)E-GEOD-24579.processed.1.zip
Array designA-AGIL-28.adf.txt
Links