The anti-inflammatory function of adenine occurs through AMPK activation and its downstream transcriptional regulation in THP-1 cells

Abstract

Pathogenic bacteria induced sepsis is a risk factor for hospital mortality. Monocyte-derived inflammatory cytokines participate in the sepsis progression. The anti-inflammatory effect of adenine has been previously reported by our laboratory and others. However, the mechanism of action has different opinions and remains unclear in monocyte. Here, adenine was found to significantly inhibit the secretion of lipopolysaccharide-induced inflammatory cytokines such as TNF-α, IL-1β and IL-6 in THP-1 cells. The bioinformatic analysis results showed that the anti-inflammatory function is possibly due to the inhibition of NF-κB signaling. And this result is confirmed by using immunocytochemistry. Moreover, this effect can be suppressed by the AMPK inhibitor. Results also showed that adenine can activate AMPK and its multiple downstream targets. Data from mass spectrometry showed that adenine promotes significant elevation of intracellular AMP. Our data indicate that the anti-inflammatory mechanism of adenine may involve adenine phosphoribosyltransferase-catalyzed intracellular AMP elevation, which stimulates AMPK activation.