In a recent article published in Science Signaling, Yuangheng He and colleagues asked how the weak alkaline compound chloroquine (CQ) enhances the anti-inflammatory effects of synthetic glucocorticoids like dexamethasone, which are used to treat a host of inflammatory and autoimmune diseases. In the process they explored the intersection of lysosomal degradation pathways and glucocorticoid receptor signaling. For these investigations, they needed tools such as reporters and protein tags that allowed sensitive and accurate detection of events in real time in a variety of cells and systems.
The work is fascinating and removes the lysosome from its pigeon-hole description of garbage can (or recycling center) of the cell and places it in the center of cell signaling. The work also is fascinating because it takes a systems-view of a biological question: How is it that the drug chloroquine just happens to influence glucocorticoid signaling? To answer this question the authors employ an amazing array of techniques and technologies to ask questions in several systems under a many different conditions. The result is a work that explains a lot, but like all good science raises new questions for us to scratch our heads over.
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 (2011). Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Science signaling, 4 (180) PMID: 21730326