Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis.

Jo D, Liu D, Yao S, Collins RD, Hawiger J
Nat Med. 2005 11 (8): 892-8

PMID: 16007096 · DOI:10.1038/nm1269

Suppressor of cytokine signaling (SOCS) 3 attenuates proinflammatory signaling mediated by the signal transducer and activator of transcription (STAT) family of proteins. But acute inflammation can occur after exposure to pathogen-derived inducers staphylococcal enterotoxin B (SEB) and lipopolysaccharide (LPS), or the lectin concanavalin A (ConA), suggesting that physiologic levels of SOCS3 are insufficient to stem proinflammatory signaling under pathogenic circumstances. To test this hypothesis, we developed recombinant cell-penetrating forms of SOCS3 (CP-SOCS3) for intracellular delivery to counteract SEB-, LPS- and ConA-induced inflammation. We found that CP-SOCS3 was distributed in multiple organs within 2 h and persisted for at least 8 h in leukocytes and lymphocytes. CP-SOCS3 protected animals from lethal effects of SEB and LPS by reducing production of inflammatory cytokines and attenuating liver apoptosis and hemorrhagic necrosis. It also reduced ConA-induced liver apoptosis. Thus, replenishing the intracellular stores of SOCS3 with CP-SOCS3 effectively suppresses the devastating effects of acute inflammation.

MeSH Terms (17)

Animals Apoptosis Concanavalin A Cytokines Enterotoxins Inflammation Leukocytes Lipopolysaccharides Liver Lymphocytes Mice Recombinant Proteins Signal Transduction Staphylococcal Infections STAT1 Transcription Factor Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins

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