PMID- 26610206 OWN - NLM STAT- MEDLINE DCOM- 20160914 LR - 20181113 IS - 2041-4889 (Electronic) VI - 6 IP - 11 DP - 2015 Nov 26 TI - A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1. PG - e1993 LID - 10.1038/cddis.2015.338 [doi] AB - 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-gamma and IL-1beta 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-alpha, IFN-gamma, IL-1beta 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. FAU - Yang, C AU - Yang C AD - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. AD - Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Y AU - Zhang Y AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. AD - Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Wang, J AU - Wang J AD - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. FAU - Li, L AU - Li L AD - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. FAU - Wang, L AU - Wang L AD - Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Hu, M AU - Hu M AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. FAU - Xu, M AU - Xu M AD - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. FAU - Long, Y AU - Long Y AD - CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. FAU - Rong, R AU - Rong R AD - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. AD - Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Zhu, T AU - Zhu T AD - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151126 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Peptides, Cyclic) RN - 0 (STAT3 Transcription Factor) RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Animals MH - Cell Differentiation MH - Dendritic Cells/*drug effects MH - Graft Rejection/*genetics MH - Janus Kinase 2/*metabolism MH - Kidney Transplantation/*adverse effects MH - Peptides, Cyclic/*pharmacology MH - Rats MH - Rats, Wistar MH - STAT3 Transcription Factor/*metabolism MH - Signal Transduction PMC - PMC4670942 EDAT- 2015/11/27 06:00 MHDA- 2016/09/15 06:00 PMCR- 2015/11/01 CRDT- 2015/11/27 06:00 PHST- 2015/07/16 00:00 [received] PHST- 2015/09/22 00:00 [revised] PHST- 2015/10/09 00:00 [accepted] PHST- 2015/11/27 06:00 [entrez] PHST- 2015/11/27 06:00 [pubmed] PHST- 2016/09/15 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - cddis2015338 [pii] AID - 10.1038/cddis.2015.338 [doi] PST - epublish SO - Cell Death Dis. 2015 Nov 26;6(11):e1993. doi: 10.1038/cddis.2015.338.