Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response.

Monosodium urate crystals (MSUc) induce inflammation in vivo without prior priming, raising the possibility of an initial cell-autonomous phase. Here, using genome-wide transcriptomic analysis and biochemical assays, we demonstrate that MSUc alone induce a metabolic-inflammatory transcriptional program in non-primed human and murine macrophages that is markedly distinct to that induced by LPS. Genes uniquely upregulated in response to MSUc belong to lipid and amino acid metabolism, glycolysis, and SLC transporters.

Can Metabolic Pathways Be Therapeutic Targets in Rheumatoid Arthritis?

The metabolic rewiring of tumor cells and immune cells has been viewed as a promising source of novel drug targets. Many of the molecular pathways implicated in rheumatoid arthritis (RA) directly modify synovium metabolism and transform the resident cells, such as the fibroblast-like synoviocytes (FLS), and the synovial tissue macrophages (STM), toward an overproduction of enzymes, which degrade cartilage and bone, and cytokines, which promote immune cell infiltration. Recent studies have shown metabolic changes in stromal and immune cells from RA patients.