TSG-6 protein expression in the pancreatic islets of NOD mice
- 171 Downloads
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.
KeywordsType 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.)
- Bayliss MT, Howat SLT, Dudhia J, Murphy JM, Barry FP, Edwards JC, Day AJ (2001) Up-regulation and differential expression of hyaluronan-binding protein TSG-6 in cartilage and synovium in rheumatoid arthritis and osteoarthritis. Osteoarthritis Cartilage 9:42–48. doi: 10.1053/joca.2000.0348 PubMedCrossRefGoogle Scholar
- Fülöp C, Kamath RV, Li Y, Otto JM, Salustr A, Olsen BR, Glant TT, Hascall VC (1997) Coding sequence, exon-intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes. Gene 202:95–102. doi: 10.1016/S0378-1119(97)00459-9 PubMedCrossRefGoogle Scholar
- Lee LF, Xu B, Michie SA, Beilhack GF, Warganich T, Turley S, McDevitt HO (2005) The role of TNFα in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: analysis of dendritic cell maturation. Proc Natl Acad Sci USA 102:15995–16000. doi: 10.1073/pnas.0508122102 PubMedCrossRefGoogle Scholar
- Mindrescu C, Thorbecke GJ, Klein MJ, Vilček J, Wisniewski HG (2000) Amelioration of collagen-induced arthritis in DBA/1 J mice by recombinant TSG-6, a tumor necrosis factor/interleukin-1-inducible protein. Arthritis Rheum 43:2668–2677. doi:10.1002/1529-0131(200012)43:12<2668::AID-ANR6>3.0.CO;2-EPubMedCrossRefGoogle Scholar
- Parkar AA, Kahmann JD, Howat SLT, Bayliss MT, Day AJ (1998) TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage. FEBS Lett 428:171–176. doi: 10.1016/S0014-5793(98)00523-7 PubMedCrossRefGoogle Scholar