Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis
<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is widely recognized as an essential element in the triggering of innate immunity, binding pathogen-associated molecules such as Lipopolysaccharide (LPS), and in initiating a cascade of pro-inflammatory ev...
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doaj-b10ed19302674351af9457d07204a2412020-11-25T03:42:49ZengBMCBMC Immunology1471-21722011-02-011211810.1186/1471-2172-12-18Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasisSantos Icaro AMantovani MarluceMourão Roberta FGaray-Malpartida Humberto MSogayar Mari CGoldberg Anna C<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is widely recognized as an essential element in the triggering of innate immunity, binding pathogen-associated molecules such as Lipopolysaccharide (LPS), and in initiating a cascade of pro-inflammatory events. Evidence for TLR4 expression in non-immune cells, including pancreatic β-cells, has been shown, but, the functional role of TLR4 in the physiology of human pancreatic β-cells is still to be clearly established. We investigated whether TLR4 is present in β-cells purified from freshly isolated human islets and confirmed the results using MIN6 mouse insulinoma cells, by analyzing the effects of TLR4 expression on cell viability and insulin homeostasis.</p> <p>Results</p> <p>CD11b positive macrophages were practically absent from isolated human islets obtained from non-diabetic brain-dead donors, and TLR4 mRNA and cell surface expression were restricted to β-cells. A significant loss of cell viability was observed in these β-cells indicating a possible relationship with TLR4 expression. Monitoring gene expression in β-cells exposed for 48h to the prototypical TLR4 ligand LPS showed a concentration-dependent increase in TLR4 and CD14 transcripts and decreased insulin content and secretion. TLR4-positive MIN6 cells were also LPS-responsive, increasing TLR4 and CD14 mRNA levels and decreasing cell viability and insulin content.</p> <p>Conclusions</p> <p>Taken together, our data indicate a novel function for TLR4 as a molecule capable of altering homeostasis of pancreatic β-cells.</p> http://www.biomedcentral.com/1471-2172/12/18 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Santos Icaro A Mantovani Marluce Mourão Roberta F Garay-Malpartida Humberto M Sogayar Mari C Goldberg Anna C |
spellingShingle |
Santos Icaro A Mantovani Marluce Mourão Roberta F Garay-Malpartida Humberto M Sogayar Mari C Goldberg Anna C Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis BMC Immunology |
author_facet |
Santos Icaro A Mantovani Marluce Mourão Roberta F Garay-Malpartida Humberto M Sogayar Mari C Goldberg Anna C |
author_sort |
Santos Icaro A |
title |
Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis |
title_short |
Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis |
title_full |
Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis |
title_fullStr |
Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis |
title_full_unstemmed |
Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis |
title_sort |
toll-like receptor 4 (tlr4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis |
publisher |
BMC |
series |
BMC Immunology |
issn |
1471-2172 |
publishDate |
2011-02-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is widely recognized as an essential element in the triggering of innate immunity, binding pathogen-associated molecules such as Lipopolysaccharide (LPS), and in initiating a cascade of pro-inflammatory events. Evidence for TLR4 expression in non-immune cells, including pancreatic β-cells, has been shown, but, the functional role of TLR4 in the physiology of human pancreatic β-cells is still to be clearly established. We investigated whether TLR4 is present in β-cells purified from freshly isolated human islets and confirmed the results using MIN6 mouse insulinoma cells, by analyzing the effects of TLR4 expression on cell viability and insulin homeostasis.</p> <p>Results</p> <p>CD11b positive macrophages were practically absent from isolated human islets obtained from non-diabetic brain-dead donors, and TLR4 mRNA and cell surface expression were restricted to β-cells. A significant loss of cell viability was observed in these β-cells indicating a possible relationship with TLR4 expression. Monitoring gene expression in β-cells exposed for 48h to the prototypical TLR4 ligand LPS showed a concentration-dependent increase in TLR4 and CD14 transcripts and decreased insulin content and secretion. TLR4-positive MIN6 cells were also LPS-responsive, increasing TLR4 and CD14 mRNA levels and decreasing cell viability and insulin content.</p> <p>Conclusions</p> <p>Taken together, our data indicate a novel function for TLR4 as a molecule capable of altering homeostasis of pancreatic β-cells.</p> |
url |
http://www.biomedcentral.com/1471-2172/12/18 |
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