Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis.
| Autor: | Garay-Malpartida HM; Núcleo de Terapia Celular e Molecular, Universidade de São Paulo, São Paulo, Brasil., Mourão RF, Mantovani M, Santos IA, Sogayar MC, Goldberg AC |
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| Jazyk: | angličtina |
| Zdroj: | BMC immunology [BMC Immunol] 2011 Feb 28; Vol. 12, pp. 18. Date of Electronic Publication: 2011 Feb 28. |
| DOI: | 10.1186/1471-2172-12-18 |
| Abstrakt: | Background: 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. Results: 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. Conclusions: Taken together, our data indicate a novel function for TLR4 as a molecule capable of altering homeostasis of pancreatic β-cells. (© 2011 Garay-Malpartida et al; licensee BioMed Central Ltd.) |
| Databáze: | MEDLINE |
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