Intracellular delivery of a cell-penetrating SOCS1 that targets IFN-gamma signaling.

ABSTRACT: Suppressor of cytokine signaling-1 (SOCS1) is an intracellular inhibitor of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway that couples interferon-gamma (IFN-gamma) signaling to the nucleus. Because several inflammatory diseases are associated with uncontrolled IFN-gamma signaling, we engineered a recombinant cell-penetrating SOCS1 (CP-SOCS1) to target this pathway. Here, we show that CP-SOCS1, analogous to endogenous SOCS1, interacted with components of the IFN-gamma signaling complex and functionally attenuated the phosphorylation of STAT1, which resulted in the subsequent inhibition of the production of proinflammatory chemokines and cytokines. Thus, controlled, intracellular delivery of recombinant CP-SOCS1 boosted the anti-inflammatory potential o

SUBMITTER: DiGiandomenico A 

PROVIDER: S-EPMC2798805 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature