ABSTRACT
Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-kappaB) translocation.
Subject(s)
Humans , Apoptosis , Autoimmune Diseases , Caspase 3 , Cell Death , Gene Expression , NF-kappa B , Peptide Hydrolases , Physiology , Receptors, Death Domain , RNA, Small Interfering , Signal Transduction , T-Lymphocytes , TNF Receptor-Associated Factor 4 , Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsABSTRACT
Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic beta-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic beta-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic beta-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic beta-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic beta cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.
Subject(s)
Autoimmunity , Down-Regulation , Glucose , Homeostasis , Immune System , Insulin-Secreting Cells , Interleukin-6 , Islets of Langerhans , Macrophages , Nitric Oxide , PeroxiredoxinsABSTRACT
We experienced a case of congenital goiter with congenital hypothyroidism in 45 day-old male, who complained of respiratory difficulty and anterior neck mass. After admission, he was diagnosed congenital hypothyroidism by the clinical manifestations and laboratory tests including biochemistry, radioimmunoassay, radioisotope study, perchlorate discharge test, and bone radiography. We obtained positive finding at the perchlorate discharge test and found that his congenital goiter with congenital hypothyroidism was manifested by organification defect. We started treatment with L-thyroxine orally at 6th hospital day. The case was presented with brief review of literatures.