title: High glucose increases LPS-induced DC apoptosis through modulation of ERK1/2, AKT and Bax/Bcl-2.
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.
authors.forename: Mei
authors.initials: M
authors.lastname: Feng
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.forename: Yulian
authors.initials: Y
authors.lastname: Jiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Ju
authors.affiliation: Central Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China. yanshu_2004@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Yueran
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007150:Immunohistochemistry; D007422:Intestines / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000187:drug effects* / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose