Hyperglycemia, oxidative and nitrosative stress affect antiviral, inflammatory and apoptotic signaling of cultured thymocytes.
A high prevalence of various infectious diseases is reported in diabetic patients, which may suggest impaired innate immunity against different pathogen-associated molecular patterns. This study investigated the effects of hyperglycemia, oxidative stress (H(2)O(2)), nitric oxide (NO) and peroxynitrite (ONOO(-)) on the modulation of antiviral (MDA-5, IRF-3 and phospho-IRF-3), inflammatory (NF-kappaB) and pro/anti-apoptotic molecules (Bax and Bcl-2) in BALB/c mice thymocytes. Each of the experimental conditions, except the weakest NO concentration, resulted in down-regulation of MDA-5, IRF-3 and phospho-IRF-3. In contrast, each of the experimental conditions elicited up-regulation of NF-kappaB, Bcl-2 and Bax. These results suggest that hyperglycemia, oxidative and nitrosative stress may contribute to the reduced immunity of the host by altering the MDA-5/IRF-3/phosphoIRF-3 axis, as well as contributing to the mechanisms of inflammatory reaction via increased NF-kappaB, and to augmented turnover rate of thymocyte cells via Bcl2/Bax up-regulation.
Kocic
G
G
Institute of Biochemistry, University of Nis, Serbia. kocicrg@yahoo.co.uk
Sokolovic
D
D
Jevtovic
T
T
Veljkovic
A
A
Kocic
R
R
Nikolic
G
G
Basic
J
J
Stojanovic
D
D
Cencic
A
A
Stojanovic
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006943:Hyperglycemia / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide