Protection of NIT-1 pancreatic beta-cells from immune attack by inhibition of NF-kappa B
- Author(s)
- Stephens, LA; Thomas, HE; Kay, TWH;
- Details
- Publication Year 1997-06,Volume 10,Issue #3,Page 293-298
- Journal Title
- JOURNAL OF AUTOIMMUNITY
- Publication Type
- Journal Article
- Abstract
- We have recently observed that inhibition of NF-kappa B in NIT-1 insulinoma cells protects them from tumour necrosis factor (TNF)-induced cell death in vitro, possibly because expression of interleukin-1 (IL-1)beta-converting enzyme (ICE), a member of the cysteine protease pathway of cell death, is decreased. In the current study we have examined the effect of the same inhibitor of NF-kappa B on class I major histocompatibility complex (MHC) protein expression in NIT-1 cells and shown that inhibition of NF-kappa B activation decreased basal and TNF-induced class I MHC levels. Although inducible nitric oxide synthase (iNOS) may also be inhibited by inhibition of NF-kappa B, this could not be demonstrated in NIT-1/Delta sp cells because wild-type NIT-1 cells express very little iNOS. When NIT-1/Delta sp12 cells, expressing high levels of the NF-kappa B inhibitor, are transplanted into immunodeficient NOD/scid mice, tumorigenesis and death by hypoglycemia proceed similarly to untransfected NIT-1 cells. Untransfected NIT-1 cells were killed by co-transfer of splenic T cells from diabetic but not non-diabetic NOD mice. NIT-1/Delta sp12 cells were protected from killing in vivo by T cells from diabetic mice, in that tumours developed in four out of five mice and the kinetics of tumour development were not significantly delayed. NIT-1/Delta sp12 cells were not protected from killing by T cells from mice previously primed with NIT-1 cells. In conclusion, inhibition of NF-kappa B is likely to suppress several different pathways of immune-mediated cell death in beta-cells and protects NIT-1 cells from immune attack by diabetogenic T cells in vivo. Inhibition of NF-kappa B is a potentially effective strategy for protection of pancreatic beta-cells in autoimmune diabetes. (C) 1997 Academic Press Limited.
- Publisher
- ACADEMIC PRESS LTD
- Keywords
- NONOBESE DIABETIC MICE; NOD MICE; T-CELL; INSULITIS; ANTIGENS; MOUSE
- Publisher's Version
- https://doi.org/10.1006/jaut.1997.0133
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1997-06-01 12:00:00