Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via exosomes and its anti-apoptotic effect.
It has been reported that the effect of inflammatory cytokines on β-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 β-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 β-cells from apoptosis induced by a high level of inflammatory cytokines.
['Zhu|Qun|Q|', 'Kang|Jian|J|', 'Miao|Heng|H|', 'Feng|Yamin|Y|', 'Xiao|Lijun|L|', 'Hu|Zhigao|Z|', 'Liao|Duan-Fang|DF|', 'Huang|Yan|Y|', 'Jin|Junfei|J|', 'He|Songqing|S|']
D000818:Animals D017209:Apoptosis D015153:Blotting, Western D002460:Cell Line D055572:Ceramidases D003470:Culture Media D016207:Cytokines D004305:Dose-Response Relationship, Drug D004591:Electrophoresis, Polyacrylamide Gel D004797:Enzyme-Linked Immunosorbent Assay D055354:Exosomes D007515:Islets of Langerhans D051381:Rats
neutral ceramidase exosome cytokine β-cell apoptosis