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

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-1ß 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.

Differential proteomics of monosodium urate crystals-induced inflammatory response in dissected murine air pouch membranes by iTRAQ technology.

The precipitation of monosodium urate crystals within joints triggers an acute inflammatory reaction that is the root cause of gout. The inflammation induced by the injection of MSU crystals into the murine air pouch for 1, 3, and 5 h was examined by iTRAQ-based proteomic profiling. The iTRAQ-labeled peptides were fractionated by SCX, basic-RP or solution-IEF, followed by LC-MS/MS analysis. A total of 951 proteins were quantified from the total combined fractions. Among them, 317 proteins exhibited a differential expression, compared to that of the controls at one time point or more. The majority of the differentially expressed proteins were found in the sample after a 5-h MSU treatment. Western blot revealed that the expression levels of cathelin-related antimicrobial peptide and S100A9 were positively correlated with the time-course treated with MSU. Further analysis of GeneGO pathway demonstrated that these differentially expressed proteins are primarily related to the immune-related complement system and the tricarboxylic acid cycle. Moreover, seven genes from the TCA cycle were found to be significantly downregulated at the transcriptional level and its correlation with gout and possible therapeutic applications are worth further investigation. Last, we found that pyruvate carboxylation could be potential targets for antigout treatment.