title: Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via exosomes and its anti-apoptotic effect.
abstract: 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.
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Heng
authors.initials: H
authors.lastname: Miao
authors.forename: Yamin
authors.initials: Y
authors.lastname: Feng
authors.forename: Lijun
authors.initials: L
authors.lastname: Xiao
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Hu
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Junfei
authors.initials: J
authors.lastname: Jin
authors.forename: Songqing
authors.initials: S
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D055572:Ceramidases / Q000378:metabolism*; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology; D051381:Rats
chemical_list: D003470:Culture Media; D016207:Cytokines; D055572:Ceramidases
keywords: apoptosis; cytokine; exosome; neutral ceramidase; β-cell