Tumor necrosis factor-alpha-activated cell death pathways in NIT-1 insulinoma cells and primary pancreatic beta cells
- Author(s)
- Stephens, LA; Thomas, HE; Ming, L; Grell, M; Darwiche, R; Volodin, L; Kay, TWH;
- Details
- Publication Year 1999-07,Volume 140,Issue #7,Page 3219-3227
- Journal Title
- ENDOCRINOLOGY
- Publication Type
- Journal Article
- Abstract
- Tumor necrosis factor-alpha (TNF alpha) is a potential mediator of beta cell destruction in insulin-dependent diabetes mellitus. We have studied TNF-responsive pathways leading to apoptosis in beta cells. Primary beta cells express low levels of the type I TNF receptor (TNFR1) but do not express the type 2 receptor (TNFR2). Evidence for TNFR1 expression on beta cells came from flow cytometry using monoclonal antibodies specific for TNFR1 and TNFR2 and from RT-PCR of beta cell RNA. NIT-1 insulinoma cells similarly expressed TNFR1 (at higher levels than primary beta cells) as detected by flow cytometry and radio-binding studies. TNF induced NF-kappa B activation in both primary islet cells and NIT-1 cells. Apoptosis in response to TNF alpha was observed in NIT-I cells whereas apoptosis of primary beta cells required both TNF alpha and interferon-gamma (IFN gamma). Apoptosis could be prevented in NIT-1 cells by expression of dominant negative Pas-associating protein with death domain (dnFADD). Apoptosis in NIT-1 cells was increased by coincubation with IFN gamma, which also increased caspase 1 expression. These data show that TNF-activated pathways capable of inducing apoptotic cell death are present in beta cells. Caspase activation is the dominant pathway of TNF-induced cell death in NIT-1 cells and may be an important mechanism of beta cell damage in insulin-dependent diabetes mellitus.
- Publisher
- ENDOCRINE SOC
- Keywords
- INTERLEUKIN-1-BETA CONVERTING-ENZYME; FACTOR-INDUCED APOPTOSIS; NONOBESE DIABETIC MICE; NITRIC-OXIDE SYNTHASE; TNF-ALPHA; FACTOR RECEPTOR; MEDIATED APOPTOSIS; T-LYMPHOCYTES; DNA-DAMAGE; NOD MOUSE
- Publisher's Version
- https://doi.org/10.1210/en.140.7.3219
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-07-01 12:00:00