Journal of Molecular Histology

, Volume 39, Issue 6, pp 585–593 | Cite as

TSG-6 protein expression in the pancreatic islets of NOD mice

  • M. Kvezereli
  • S. A. Michie
  • T. Yu
  • R. J. Creusot
  • M. J. Fontaine
Original Paper


The histologic hallmark of the development of type 1 diabetes (T1D) is insulitis, characterized by leukocytic infiltration of the pancreatic islets. The molecules controlling the early influx of leukocytes into the islets are poorly understood. Tumor necrosis factor α (TNFα)-stimulated gene 6 (TSG-6) is involved in inflammation, extracellular matrix formation, cell migration, and development. In the present study, we examined the expression and cellular localization of TSG-6 protein in islets of female non-obese diabetic (NOD) mice using frozen section immunofluorescence staining. Pancreata from nondiabetic (8 and 25 weeks old), prediabetic (230–280 mg/dl blood glucose) and diabetic (>300 mg/dl blood glucose) NOD mice were stained for TSG-6, insulin, CD3, CD11c, Mac3 and CD31. TSG-6 protein was detected in 67% of islets of prediabetic mice, 27% of islets of 25-week old nondiabetic mice, and less than 7% of islets of diabetic mice and 8-week old nondiabetic mice. Lastly, islet-derived TSG-6 protein was localized to the infiltrating CD3 and CD11c positive leukocytes.


Type 1 diabetes Insulitis Inflammation TSG-6 Dendritic cells T lymphocytes 



We would like to acknowledge Dr. C. Garrison Fathman for providing us with lentiviral plasmids, Anet James for assistance with the artwork, and Claudia Benike and Donna Jones for critical reviews of the manuscript. We would like to thank Dr. Edgar Engleman for making all the necessary laboratory equipment accessible.

This work was supported by:

Dean’s Postdoctoral Fellowship, Stanford University (to M.K.)

Department of Pathology Research Fund at Stanford (to M.J.F.)

Juvenile Diabetes Research Foundation Grant 1-2001-56 (to S.A.M.)

National Institutes of Health Grant R01 DK67592 (to S.A.M.)

Juvenile Diabetes Research Foundation Postdoctoral Fellowship (to R.J.C.)

Supplementary material

10735_2008_9199_MOESM1_ESM.jpg (69 kb)
MOESM1 [TSG-6 gene fragment amplified by PCR. Lane 1 shows DNA markers, Lane 2 indicates 851 bp fragment of the TSG-6 gene] (JPG 68 kb)
10735_2008_9199_MOESM2_ESM.jpg (3.4 mb)
MOESM2 [Immunoblotting of TSG-6 protein in lentiviral-transduced 293T cells. Lane 1 is 35 kDa recombinant TSG-6 protein as a positive control, Lane 2 is untransduced 293T cells, Lane 3 is 293T cells transduced with GFP only expressing-lentivirus, Lanes 4 and 5 are 293T cells transduced with TSG-6 GFP lentivirus at multiplicity of infection of 10 and 15, respectively] (JPG 3489 kb)


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • M. Kvezereli
    • 1
  • S. A. Michie
    • 1
  • T. Yu
    • 1
  • R. J. Creusot
    • 2
  • M. J. Fontaine
    • 1
  1. 1.Department of PathologyStanford University School of MedicineStanfordUSA
  2. 2.Department of MedicineStanford University School of MedicineStanfordUSA

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