Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response
| Autor: | Isidoro Cobo, Anyan Cheng, Jessica Murillo-Saich, Roxana Coras, Alyssa Torres, Yohei Abe, Addison J. Lana, Johannes Schlachetzki, Ru Liu-Bryan, Robert Terkeltaub, Elsa Sanchez-Lopez, Christopher K. Glass, Monica Guma |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Gouty SLC2A1 Medical Physiology macrophage General Biochemistry Genetics and Molecular Biology Article Vaccine Related Mice gout Biodefense Genetics 2.1 Biological and endogenous factors Animals transcriptional regulation Aetiology MSU crystals Inflammation AP-1 activation Arthritis Gouty Arthritis Prevention Inflammatory and immune system Macrophages glycolysis Uric Acid JNK Biochemistry and Cell Biology |
| Zdroj: | Cell Rep Cell reports, vol 38, iss 10 |
| ISSN: | 2211-1247 |
| Popis: | Monosodium urate crystals (MSUc) induce inflammation invivo 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. This upregulation leads to a metabolic rewiring in sera from individuals and mice with acute gouty arthritis. Mechanistically, the initiating inflammatory-metabolic changes in acute gout flares are regulated through a persistent expression and increased binding of JUN to the promoter of target genes through JNK signaling-but not P38-in a process that is different than after LPS stimulation and independent of inflammasome activation. Finally, pharmacological JNK inhibition limits MSUc-induced inflammation in animal models of acute gouty inflammation. |
| Databáze: | OpenAIRE |
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