Page 14 - M. Immunology
P. 14
[M. Immunology-10]
Regulation of JAK/STAT signaling with cell-permeable SOCS3
suppresses acute inflammatory disorders
Shinyoung Park¹, Sukyeong Jeong¹, Jaehyeon Kim¹, Chohyun Kim¹, Mikyung Kim¹, Youngsil Choi¹,
Daewoong Jo¹˙*
¹Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, South Korea
Suppressor of cytokine signaling 3 (SOCS3) binds to Janus kinase 2 (JAK2) and prevents downstream activation of
the signal transducers and activators of transcription (STAT). Prolonged exposure to inflammatory cytokines
overwhelms negative SOCS3 regulation and contributes to acute inflammatory disorders. Improved cell-permeable
(iCP) SOCS3 has been developed by fusing sequence-optimized hydrophobic cell-penetrating peptide (CPP), namely
advanced macromolecule transduction domain (aMTD), to replenish SOCS3 as inflammatory cytokine regulator into
cell and tissue. In the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model, iCP-SOCS3 attenuates
the progression of inflammatory bowel disease (IBD) by inhibiting phosphorylation of STAT3 and reducing the
number of permeable inflammatory cells and edema. iCP-SOCS3 suppresses concanavalin A (ConA)-induced
hepatitis, reducing apoptosis by 95%. Furthermore, iCP-SOCS3 also inhibits expression of pro-inflammatory
cytokines (TNF-α: 80%, IL-6: 99% and IFN-γ: 81%) and stimulates production of anti-inflammatory cytokine (IL-10:
700%). These results suggest iCP-SOCS3 targets in the pathogenesis of IBD and hepatitis so that it may provide
therapeutic effect on acute inflammatory disorder.
