A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1

doi:10.1038/cddis.2015.338

	A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1
	Yang, C.1,2,6; Zhang, Y.5,6; Wang, J.2,6; Li, L.2,6 ; Wang, L.5; Hu, M.6; Xu, M.2,6; Long, Y.3; Rong, R.2,4,6; Zhu, T.2,6
刊名	CELL DEATH & DISEASE
	2015-11
卷号	6
ISSN号	2041-4889
DOI	10.1038/cddis.2015.338
文献子类	Article
英文摘要	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-1 beta 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-1 beta 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.
资助项目	National Natural Science Foundation of China[81400752] ; National Natural Science Foundation of China[81400688] ; National Natural Science Foundation of China[81270832] ; National Natural Science Foundation of China[81270833] ; National Natural Science Foundation of China[81570674] ; National Natural Science Foundation of China[81370852] ; China Postdoctoral Science Foundation[2014M551327] ; Shanghai Postdoctoral Project - Science and Technology Commission of Shanghai Municipality[14R21410200] ; China National Science Fund for Distinguished Young Scholars[81325020] ; Science and Technology Commission of Shanghai Municipality of Zhongshan Hospital, Fudan University, China[12ZR1405500]
WOS关键词	ISCHEMIA-REPERFUSION INJURY ; NAKED CASPASE-3 SIRNA ; AUTOTRANSPLANT KIDNEYS ; ALLOGRAFT-REJECTION ; NEGATIVE REGULATION ; IMMUNE-RESPONSE ; INNATE IMMUNITY ; TRANSPLANTATION ; ERYTHROPOIETIN ; MECHANISMS
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000367155300026
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276336]
专题	药物化学研究室
通讯作者	Rong, R.
作者单位	1.Fudan Univ, Zhongshan Hosp, Dept Plast Surg, Shanghai 200433, Peoples R China; 2.Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200433, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 200031, Peoples R China; 4.Fudan Univ, Zhongshan Hosp, Dept Transfus, Shanghai 200433, Peoples R China 5.Fudan Univ, Zhongshan Hosp, Biomed Res Ctr, Shanghai 200433, Peoples R China; 6.Shanghai Key Lab Organ Transplantat, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Yang, C.,Zhang, Y.,Wang, J.,et al. A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1[J]. CELL DEATH & DISEASE,2015,6.
APA	Yang, C..,Zhang, Y..,Wang, J..,Li, L..,Wang, L..,...&Zhu, T..(2015).A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1.CELL DEATH & DISEASE,6.
MLA	Yang, C.,et al."A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1".CELL DEATH & DISEASE 6(2015).