title: A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1.
abstract: We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. Dendritic cells (DCs) play an activation role in acute rejection (AR). Thus, the present study was designed to investigate the effects of CHBP on DCs in a rat renal transplantation model. The left kidney was harvested from male Lewis rats and then transplanted into male Wistar rats with or without CHBP treatment. Five successive treatment doses of CHBP after transplantation significantly ameliorated AR with lower histological injury, apoptosis and CD4(+) and CD8(+) T-cell infiltration in renal allografts. CHBP reduced IFN-γ and IL-1β levels but increased IL-4 and IL-10 levels in the serum. The number of mature DCs was significantly decreased in renal allografts treated with CHBP. In addition, incubating DCs with CHBP in vitro led to reduction in TNF-α, IFN-γ, IL-1β and IL-12 levels and increase of IL-10 expression at the protein level in the supernatant. Mechanistically, CHBP inhibited TLR activation-induced DC maturation by increasing SOCS1 expression through Jak-2/STAT3 signaling. In conclusion, CHBP suppresses renal allograft AR by inhibiting the maturation of DCs via Jak-2/STAT3/SOCS1 signaling, suggesting that CHBP may be an potential therapeutic drug for treating renal AR.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.|Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.|Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.|Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: R
authors.initials: R
authors.lastname: Rong
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects*; D006084:Graft Rejection / Q000235:genetics*; D053614:Janus Kinase 2 / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010456:Peptides, Cyclic; D050796:STAT3 Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2