Research ArticlePharmacology

Identification of a Lysosomal Pathway That Modulates Glucocorticoid Signaling and the Inflammatory Response

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Science Signaling  05 Jul 2011:
Vol. 4, Issue 180, pp. ra44
DOI: 10.1126/scisignal.2001450

Targeting Lysosomes to Limit Inflammation

Chloroquine, which inhibits lysosome function, is best known for its use as an antimalarial agent. However, it has also been clinically used to treat inflammation. He et al. showed that agents that inhibit lysosome function or biogenesis promoted glucocorticoid-mediated regulation of gene expression and that this enhancement of glucocorticoid signaling was associated with an increase in the stability and abundance of the glucocorticoid receptor. Other receptors of the nuclear receptor family, but not other transcription factors, were also stabilized by inhibition of lysosomal function, suggesting that a lysosomal pathway contributes to the degradation of this family of receptors and may present a target for development of treatment strategies for autoimmune and inflammatory diseases, as well as diseases associated with aberrant nuclear receptor signaling.