ABSTRACT
The autoimmunity of type 1 diabetes is associated with T-cell hyperactivity. Current study was designed to examine the effect of circulating ribonucleic acids (RNAs), isolated from type 1 diabetic patients on proliferative, apoptotic and inflammatory potential of rat thymocytes. Rat thymocytes were assayed for proliferating nuclear cell antigen (PCNA), Bcl-2, Bax and NF-κB level, using the flow cytometric and fluorometric assays. Cells were allocated into groups, treated with RNAs purified from plasma of juvenile diabetics, adult type 1 diabetic patients, control healthy children, healthy adult persons, nucleic acids and polynucleotide standards (RNA, polyC, PolyA, PolyIC, and CpG). The upregulation of PCNA and Bcl-2 protein and downregulation of Bax protein and NF-κB was shown when the thymocytes where incubated with RNA purified from plasma of juvenile type 1 diabetic patients. The dysregulation of inflammatory cascade and central tolerance may be a defect in autoimmune diseases related to innate immunity leading to corresponding alteration in adaptive immune response.
Subject(s)
Diabetes Mellitus, Type 1/blood , RNA/blood , RNA/pharmacology , Thymus Gland/cytology , Adolescent , Adult , Animals , Cell Proliferation/drug effects , Cells, Cultured , Child , Child, Preschool , Concanavalin A/pharmacology , Deoxycytosine Nucleotides/pharmacology , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/pharmacology , Diabetes Mellitus, Type 1/genetics , Humans , Male , Middle Aged , NF-kappa B/metabolism , Oligonucleotides/blood , Oligonucleotides/isolation & purification , Oligonucleotides/pharmacology , Plasma/chemistry , Poly I-C/pharmacology , Polyribonucleotides/pharmacology , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA/isolation & purification , RNA, Ribosomal/pharmacology , Rats , Rats, Wistar , Thymus Gland/drug effects , Young Adult , bcl-2-Associated X Protein/metabolismABSTRACT
Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.
