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

Abstract

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.

The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics

“…Researchers have made the first ingenious use of animal gout models to explore the protein profiles expressed during gout attacks. Chiu et al (2015) injected sodium urate crystals into the murine air pouch (which resembles the synovial membrane) to induce inflammation. Based on proteomic analysis, the differentially expressed proteins participated in the alternative complement pathway.…”

S100A8/A9 in Inflammation

“…However, S100A9 is not a direct activator of cytokine expression in human neutrophils, but it potentiates IL-8 secretion induced by other neutrophil activators including fMLP and GM-CSF, following NF-κB, CREB-1, and STAT3/STAT5 activation ( 73 ). In addition, treating human monocytes with S100A9 increases the secretion of IL-1β, IL-6, and TNF-α in a process intimately linked to ROS generation ( 74 ). In a murine arthritis model, treatment with anti-S100A9 antibodies diminishes pro-inflammatory cytokine levels both in joints and in serum and preserves bone/collagen integrity ( 75 ).…”

Neutrophil Extracellular Vesicles: A Delicate Balance between Pro-Inflammatory Responses and Anti-Inflammatory Therapies

“…S100A8/A9 have been shown to increase the expression of CD11b/CD18 at the rolling neutrophil cell surface and ICAM-1 on endothelial cells, facilitating the interaction between both cell types and thus neutrophil diapedesis [ 86 , 87 , 88 ]. Closely related to their DAMP properties, S100A8/A9 can efficiently promote the expression and secretion of proinflammatory mediators by diverse cell types [ 83 , 89 , 90 , 91 , 92 , 93 ], probably via MyD88-dependant TLR4 signaling, resulting in the activation of NF-κB [ 89 , 94 ].…”