Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis

BMC Immunology

Research Article

Roberta F Mourão¹  Icaro A Santos¹  Humberto M Garay-Malpartida²  Anna C Goldberg³  Marluce Mantovani⁴  Mari C Sogayar⁴ 

[1] Núcleo de Terapia Celular e Molecular, Universidade de São Paulo, São Paulo, Brasil;Núcleo de Terapia Celular e Molecular, Universidade de São Paulo, São Paulo, Brasil;Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, Brasil;Núcleo de Terapia Celular e Molecular, Universidade de São Paulo, São Paulo, Brasil;Instituto de Investigação em Imunologia (iii), Institutos Nacionais de Ciência e Tecnologia, Brasil;Hospital Israelita Albert Einstein, São Paulo, Brasil;Núcleo de Terapia Celular e Molecular, Universidade de São Paulo, São Paulo, Brasil;Instituto de Química, Departamento de Bioquímica, Universidade de São Paulo, São Paulo, Brasil;

关键词: TLR4 Expression;    Human Islet;    Insulin Content;    Triple Staining;    CD14 mRNA Level;   

DOI  :  10.1186/1471-2172-12-18

 received in 2010-11-23, accepted in 2011-02-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundToll-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.ResultsCD11b 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.ConclusionsTaken together, our data indicate a novel function for TLR4 as a molecule capable of altering homeostasis of pancreatic β-cells.

【 授权许可】

Unknown   
© Garay-Malpartida et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.