PMID- 24798654
OWN - NLM
STAT- MEDLINE
DCOM- 20140815
LR  - 20211021
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 281
IP  - 12
DP  - 2014 Jun
TI  - Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via 
      exosomes and its anti-apoptotic effect.
PG  - 2861-70
LID - 10.1111/febs.12826 [doi]
AB  - It has been reported that the effect of inflammatory cytokines on beta-cell 
      destruction in type 1 diabetes is concentration-dependent. However, the 
      underlying mechanisms remain unclear. In the present study, we found that a high 
      concentration of cytokines promoted apoptosis in the rat beta-cell line INS-1, 
      whereas a low concentration of cytokines had no effect. We also found that 
      cytokines at a low concentration stimulated neutral ceramidase (NCDase) release 
      via exosomes from INS-1 cells, whereas cytokines at a high concentration 
      inhibited NCDase release. Furthermore, the results showed that the 
      NCDase-containing exosomes isolated from the culture medium of INS-1 cells 
      treated with cytokines at a low concentration inhibited apoptosis induced by a 
      high concentration of cytokines. Finally, the results also showed that the 
      protective action of NCDase in the exosomes on apoptosis was mediated by the 
      generation of sphingosine 1-phosphate (S1P) and its interaction with S1P receptor 
      2. Taken together, these findings revealed a novel NCDase-S1P-phosphate-S1P 
      receptor 2-dependent mechanism by which a low level of inflammatory cytokines 
      protects pancreatic beta-cells from apoptosis induced by a high level of 
      inflammatory cytokines.
CI  - (c) 2014 FEBS.
FAU - Zhu, Qun
AU  - Zhu Q
AD  - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical 
      University, Jiangsu, China.
FAU - Kang, Jian
AU  - Kang J
FAU - Miao, Heng
AU  - Miao H
FAU - Feng, Yamin
AU  - Feng Y
FAU - Xiao, Lijun
AU  - Xiao L
FAU - Hu, Zhigao
AU  - Hu Z
FAU - Liao, Duan-Fang
AU  - Liao DF
FAU - Huang, Yan
AU  - Huang Y
FAU - Jin, Junfei
AU  - Jin J
FAU - He, Songqing
AU  - He S
LA  - eng
GR  - I01 BX000854/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140515
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Culture Media)
RN  - 0 (Cytokines)
RN  - EC 3.5.1.23 (Ceramidases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Ceramidases/*metabolism
MH  - Culture Media
MH  - Cytokines/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Exosomes/*metabolism
MH  - Islets of Langerhans/*drug effects/enzymology
MH  - Rats
OTO - NOTNLM
OT  - apoptosis
OT  - cytokine
OT  - exosome
OT  - neutral ceramidase
OT  - beta-cell
EDAT- 2014/05/07 06:00
MHDA- 2014/08/16 06:00
CRDT- 2014/05/07 06:00
PHST- 2013/12/07 00:00 [received]
PHST- 2014/04/14 00:00 [revised]
PHST- 2014/04/28 00:00 [accepted]
PHST- 2014/05/07 06:00 [entrez]
PHST- 2014/05/07 06:00 [pubmed]
PHST- 2014/08/16 06:00 [medline]
AID - 10.1111/febs.12826 [doi]
PST - ppublish
SO  - FEBS J. 2014 Jun;281(12):2861-70. doi: 10.1111/febs.12826. Epub 2014 May 15.