Circulating nucleic acids in type 1 diabetes may modulate the thymocyte turnover rate

Cell Immunol. 2010;266(1):76-82. doi: 10.1016/j.cellimm.2010.08.016. Epub 2010 Sep 9.

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.

MeSH terms

  • 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 / blood*
  • 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 / blood*
  • RNA / isolation & purification
  • RNA / pharmacology*
  • RNA, Ribosomal / pharmacology
  • Rats
  • Rats, Wistar
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects
  • Young Adult
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Deoxycytosine Nucleotides
  • NF-kappa B
  • Oligonucleotides
  • Polyribonucleotides
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Ribosomal
  • bcl-2-Associated X Protein
  • Concanavalin A
  • deoxycytidylyl-(3'-5')-deoxyguanosine
  • RNA
  • Deoxyguanosine
  • Poly I-C