Research ArticleImmunology

Intracellular Delivery of a Cell-Penetrating SOCS1 that Targets IFN-γ Signaling

Science Signaling  21 Jul 2009:
Vol. 2, Issue 80, pp. ra37
DOI: 10.1126/scisignal.1162191

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Selective Inhibition

Interferon-γ (IFN-γ) activates the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway to stimulate the production of the proinflammatory mediators that are required for an appropriate immune response. Defects in a required negative regulatory mechanism mediated by suppressor of cytokine signaling (SOCS) proteins are implicated in chronic inflammatory conditions. DiGiandomenico et al. engineered a cell-penetrating form of SOCS1 (CP-SOCS1) expressed in a human cell line that specifically targeted STAT1 to block IFN-γ–induced production of proinflammatory cytokines and chemokines by macrophages. The application of cell-penetrating proteins produced in human cells has advantages both for research and for potential clinical applications over recombinant proteins purified from bacteria. In addition, CP-SOCS1 may provide a therapeutic strategy against inflammatory diseases.