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. 2013 Jul 19;15(4):179–184. doi: 10.1179/174329210X12650506623564

Hyperglycemia, oxidative and nitrosative stress affect antiviral, inflammatory and apoptotic signaling of cultured thymocytes

G Kocic 1, D Sokolovic 2, T Jevtovic 2, A Veljkovic 2, R Kocic 3, G Nikolic 4, J Basic 2, D Stojanovic 5, A Cencic 6, S Stojanovic 2
PMCID: PMC7067329  PMID: 20663294

Abstract

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 (H2O2), nitric oxide (NO) and peroxynitrite (ONOO–) on the modulation of antiviral (MDA-5, IRF-3 and phospho-IRF-3), inflammatory (NF-κB) 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-κB, 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-κB, and to augmented turnover rate of thymocyte cells via Bcl2/Bax up-regulation.

Keywords: OXIDATIVE STRESS, PEROXYNITRITE, GLUCOSE, IRF-3, PHOSPHO-IRF-3, MDA-5, NF-κB, BCL-2, BAX, THYMOCYTE

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