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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

BMC Gastroenterology 1/2014

High glucose increases LPS-induced DC apoptosis through modulation of ERK1/2, AKT and Bax/Bcl-2

Zeitschrift:
BMC Gastroenterology > Ausgabe 1/2014
Autoren:
Mei Feng, Juan Li, Jun Wang, Chunyan Ma, Yulian Jiao, Yan Wang, Jie Zhang, Qiuying Sun, Ying Ju, Ling Gao, Yueran Zhao
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1471-230X-14-98) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

MF conceived and designed the experiments, carried out the experimental work and drafted the manuscript. JL carried out the flow cytometry and statistical analysis. JW took care of and obtained samples from mice. CM carried out protein detection and statistical analysis. YJ participated in analysis and interpretation of results. YW participated in analysis and interpretation of results. JZ contributed reagents and materials. QS performed data collection and statistical analysis. YJ contributed materials and drafted the manuscript. LG participated in paper design and coordination and helped to draft the manuscript. YZ participated in paper design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Abstract

Background

This study investigates the effect of glucose on the LPS-induced apoptosis of dendritic cells in the intestinal tract of mice and the dendritic cell line DC2.4.

Methods

Flow cytometry was used to detect dendritic cell apoptosis both in vivo and in vitro. Hoechst 33258 staining was used to detect the morphological changes characteristic of apoptotic nuclei. Expression of apoptosis related proteins was investigated by western blot analysis and immunohistochemistry.

Results

Pretreatment with a high concentration of glucose increased apoptosis of LPS-treated dendritic cells both in vivo and in vitro at 24 h. No effect was evident at the earlier time points of 15 min and 6 h in vitro. Furthermore, at 24 hours the expression of the survival proteins AKT, ERK and Bcl-2 was decreased, while the expression of the proapoptotic protein Bax was increased. AKT, ERK, Bcl-2 and Bax were mainly located in the cytoplasm by immunohistochemistry.

Conclusions

These results suggest that high glucose concentrations might prime dendritic cells for apoptosis induced by LPS in the intestinal tract through upregulating the expression of Bax and downregulating the expression of AKT, ERK and Bcl-2. Therefore, this study may give clues to understanding the immunological mechanism behind gastrointestinal complications in diabetes mellitus.
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