title: Lymphoblastoid Cell Lines as a Tool to Study Inter-Individual Differences in the Response to Glucose.
abstract: BACKGROUND
  White blood cells have been shown in animal studies to play a central role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are immortalized EBV-transformed primary B-cell leukocytes that have been extensively used as a model for conditions in which white blood cells play a primary role. The purpose of this study was to investigate whether lymphoblastoid cell lines, by retaining many of the key features of primary leukocytes, can be induced with glucose to demonstrate relevant biological responses to those found in diabetic retinopathy.
  
  
  METHODS
  Lymphoblastoid cell lines were obtained from twenty-three human subjects. Differences between high and standard glucose conditions were assessed for expression, endothelial adhesion, and reactive oxygen species.
  
  
  RESULTS
  Collectively, stimulation of the lymphoblastoid cell lines with high glucose demonstrated corresponding changes on molecular, cellular and functional levels. Lymphoblastoid cell lines up-regulated expression of a panel of genes associated with the leukocyte-mediated inflammation found in diabetic retinopathy that include: a cytokine (IL-1B fold change = 2.11, p-value = 0.02), an enzyme (PKCB fold change = 2.30, p-value = 0.01), transcription factors (NFKB-p50 fold change = 2.05, p-value = 0.01), (NFKB-p65 fold change = 2.82, p-value = 0.003), and an adhesion molecule (CD18 fold change = 2.59, 0.02). Protein expression of CD18 was also increased (p-value = 2.14x10-5). The lymphoblastoid cell lines demonstrated increased adhesiveness to endothelial cells (p = 1.28x10-5). Reactive oxygen species were increased (p = 2.56x10-6). Significant inter-individual variation among the lymphoblastoid cell lines in these responses was evident (F = 18.70, p < 0.0001).
  
  
  CONCLUSIONS
  Exposure of lymphoblastoid cell lines derived from different human subjects to high glucose demonstrated differential and heterogeneous gene expression, adhesion, and cellular effects that recapitulated features found in the diabetic state. Lymphoblastoid cells may represent a useful tool to guide an individualized understanding of the development and potential treatment of diabetic complications like retinopathy.
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Michael A
authors: MA
authors: Grassi
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Vidhya R
authors: VR
authors: Rao
authors: Cellular Screening Center, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, United States of America.
authors: Siquan
authors: S
authors: Chen
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Dingcai
authors: D
authors: Cao
authors: The Biostatistics Center, George Washington University, Rockville, Maryland, United States of America.
authors: Xiaoyu
authors: X
authors: Gao
authors: The Biostatistics Center, George Washington University, Rockville, Maryland, United States of America.
authors: Patricia A
authors: PA
authors: Cleary
authors: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, United States of America.
authors: R Stephanie
authors: RS
authors: Huang
authors: Genetics and Genome Biology Research Institute, Sickkids, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors: Andrew D
authors: AD
authors: Paterson
authors: Department of Diabetes Complications and Metabolism, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.
authors: Rama
authors: R
authors: Natarajan
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Jalees
authors: J
authors: Rehman
authors: Departments of Medicine and Pharmacology Case Western Reserve University, Cleveland, Ohio, United States of America, and the Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, United States of America.
authors: Timothy S
authors: TS
authors: Kern
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018821:CD18 Antigens; D053583:Interleukin-1beta; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D005947:Glucose