Premium
A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell‐related glycolipids, sulfatide and β‐galactosylceramide
Author(s) -
Osterbye Thomas,
Funda David P.,
Fundová Petra,
Månsson JanEric,
TlaskalováHogenová Helena,
Buschard Karsten
Publication year - 2010
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1134
Subject(s) - cd14 , biology , receptor , beta cell , endocrinology , secretion , tumor necrosis factor alpha , medicine , microbiology and biotechnology , insulin , islet , biochemistry
Abstract Background T1DM is a T‐cell‐mediated autoimmune disease targeting insulin‐producing beta‐cells. Multiple factors may contribute to the development of T1DM. Among these, the metabolic state of beta‐cells and pro‐inflammatory cytokines, produced by infiltrating immune cells, have been implicated in the precipitation of T1DM. Methods and Results In this study, confocal immunofluorescence microscopy of human pancreata revealed a distinct subset of beta‐cells expressing the innate LPS co‐receptor CD14. Human islets expressed fully functional CD14 as LPS stimulation led to a dose‐dependent secretion of tumour necrosis factor (TNFα), interleukin (IL)‐1β and IL‐8, which were substantially inhibited by a blocking anti‐CD14 mAb. In addition, LPS stimulation impaired the glucose‐mediated insulin secretion in rat islets. β‐GalCer and sulfatide, glycolipids that are related to insulin processing and secretion, are possibly interacting with the CD14 receptor complex. β‐GalCer had an LPS‐like, serum‐ and CD14‐dependent effect on the induction of pro‐inflammatory cytokines in a human monocyte cell line. In contrast, the LPS‐mediated cytokine production was inhibited by sulfatide. Human islets also responded to β‐GalCer (10 µg/mL) by secreting TNFα, IL‐1β and IL‐8, whereas sulfatide partly inhibited the effect of LPS. Conclusions A subset of human beta‐cells expresses functional CD14 receptor and thus is able to recognize both exogenous bacterial (LPS) as well as endogenous ligands (e.g. glycolipids of beta‐cell origin). The CD14 expression on a subset of human beta‐cells may play a role in the innate surveillance of the endocrine environment but may also contribute to innate immune mechanisms in the early stages of beta‐cell aggression. Copyright © 2010 John Wiley & Sons, Ltd.