Abstract
We recently reported that Adenosine-5′-triphosphate (ATP) is able to inhibit the inflammatory reaction in stimulated whole blood. Many diseases, in which inflammatory reactions are involved, are associated with oxidative stress. In the present study, we therefore, investigated the effect of ATP on cytokine release in stimulated whole blood under conditions of oxidative stress, as simulated by pre-incubation of blood with hydrogen peroxide (H2O2). In the presence of H2O2, ATP at concentrations of 100 and 300 μM inhibited Tumour Necrosis factor-alpha (TNF-α) release and stimulated IL-10 release in LPS-PHA stimulated whole blood. Moreover, electron spin resonance (ESR) measurements showed that ATP and its breakdown product Adenosine-5′-diphosphate (ADP) attenuated spin trap-hydroxyl radical adduct formation in the Fenton reaction. Our results demonstrate that even in circumstances of severe oxidative stress, ATP has marked anti-inflammatory properties in stimulated whole blood. Moreover, the inhibition of the hydroxyl radical ESR signal indicates a direct attenuation of oxidative stress by ATP.
Abbreviations | ||
ADP | = | Adenosine-5′-diphosphate |
AMP | = | Adenosine-5′-monophosphate |
ATP | = | Adenosine-5′-triphosphate |
COPD | = | Chronic obstructive pulmonary disease |
DMPO | = | 5,5-dimethyl-1-pyrroline N-oxide |
ESR | = | Electron spin resonance spectroscopy |
H2O2 | = | Hydrogen peroxide |
IL-10 | = | Interleukin-10 |
IL-6 | = | Interleukin-6 |
LPS | = | Lipopolysaccharide |
NFκB | = | Nuclear factor-kappaB |
√OH | = | Hydroxyl radical |
PHA | = | Phytohemagglutinin |
ROS | = | Reactive oxygen species |
SEM | = | Standard error mean |
TLR-4 | = | Toll-like receptor 4 |
TNF-α | = | Tumor necrosis factor-alpha |
Abbreviations | ||
ADP | = | Adenosine-5′-diphosphate |
AMP | = | Adenosine-5′-monophosphate |
ATP | = | Adenosine-5′-triphosphate |
COPD | = | Chronic obstructive pulmonary disease |
DMPO | = | 5,5-dimethyl-1-pyrroline N-oxide |
ESR | = | Electron spin resonance spectroscopy |
H2O2 | = | Hydrogen peroxide |
IL-10 | = | Interleukin-10 |
IL-6 | = | Interleukin-6 |
LPS | = | Lipopolysaccharide |
NFκB | = | Nuclear factor-kappaB |
√OH | = | Hydroxyl radical |
PHA | = | Phytohemagglutinin |
ROS | = | Reactive oxygen species |
SEM | = | Standard error mean |
TLR-4 | = | Toll-like receptor 4 |
TNF-α | = | Tumor necrosis factor-alpha |