| A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell-related glycolipids, sulfatide and β-galactosylceramide. | |
| | |
MedLine Citation:
|
PMID: 20949640 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Thomas Osterbye; David P Funda; Petra Fundová; Jan-Eric Månsson; Helena Tlaskalová-Hogenová; Karsten Buschard |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-14 |
Journal Detail:
|
Title: Diabetes/metabolism research and reviews Volume: 26 ISSN: 1520-7560 ISO Abbreviation: Diabetes Metab. Res. Rev. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-02 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100883450 Medline TA: Diabetes Metab Res Rev Country: England |
Other Details:
|
Languages: eng Pagination: 656-67 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 John Wiley & Sons, Ltd. |
Affiliation:
|
Bartholin Instituttet, Rigshospitalet, Biocenter Copenhagen, Copenhagen N, Denmark. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mechanisms of genetic variation in polioviruses.
Next Document: A comparison of single-voxel clinical in vivo hepatic (31) P MR spectra acquired at 1.5 and 3.0 Tesl...