Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1

Abstract

The relationship of uric acid with macrophages has not been fully elucidated. We investigated the effect of uric acid on the proinflammatory ability of human macrophages and then examined the possible molecular mechanism involved. Primary human monocytes were differentiated into macrophages for subsequent exposure to 0, 0.23, 0.45, or 0.9 mmol/L uric acid for 12 h, in the presence or absence of 1 mmol/L probenecid. Flow cytometry was used to measure proinflammatory marker production and phagocytic activity that was quantified as a percentage of GFP-labeled Escherichia coli positive macrophages. qPCR was used to measure the macrophage expression of the urate anion transporter 1 (URAT1). As compared to control cells, the production of tumor necrosis factor-alpha (TNF-alpha), toll-like receptor 4 (TLR4), and cluster of differentiation (CD) 11c was significantly increased by uric acid. In contrast, macrophages expressing CD206, CX3C-motif chemokine receptor 1 (CX3CR1), and C-C chemokine receptor type 2 (CCR2) were significantly reduced. Uric acid progressively increased macrophage phagocytic activity and downregulated URAT1 expression. Probenecid-a non-specific blocker of URAT1-dependent uric acid transport-inhibited both proinflammatory cytokine production and phagocytic activity in macrophages that were exposed to uric acid. These results suggest that uric acid has direct proinflammatory effects on macrophages possibly via URAT1.

Immunotropic effects of so-called slag metabolites (creatinine, urea, uric acid and bilirubin) at rats

“…aureus by blood neutrophils, instead downregulating the content of rodshaped neutrophils, monocytes and natural killers in the blood. Our findings are consistent with data from Martínez-Reyes CP et al [27], which showed in vitro that incubation of human macrophages for 12 hours in the presence of increasing concentrations of uric acid (0,23; 0,45 and 0,9 mM/L, ie comparable to its level in plasma) dose-dependently increased their phagocytic activity, which was defined as the percentage of macrophages containing labeled Escherichia coli. This was accompanied by increased expression of TL4-receptors and increased production of TNF-α.…”

Usefulness of Extra Virgin Olive Oil Minor Polar Compounds in the Management of Chronic Kidney Disease Patients

“…The UA increase observed in CKD patients seems to favor OS through the inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, altering the vascular response to nitric oxide [ 61 ]. Furthermore, it seems to exert a pro-inflammatory action by activating transcription of the factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) [ 62 ] and stimulating the synthesis of tumor necrosis factor (TNF)-α and IL-1 [ 63 ]. We hypothesized that the UA reduction observed in our patients after 9 weeks of SYN consumption, may be due to two probable mechanisms.…”

Why Does Hyperuricemia Not Necessarily Induce Gout?

“…Hyperuricemia could induce an activated status of inflammation [ 51 ] or autoinflammation [ 52 ]. It could instigate inflammation by stimulating the production of inflammatory factors such as interleukin-6, interleukin-1(beta), tumor necrosis factor-alpha and CRP [ 53 ], or enhancing reactive oxygen species [ 54 ], or initiating systemic inflammation via the nuclear factor (NF)- κB signaling pathway [ 55 ], or direct proinflammatory effects on macrophages [ 56 ]. Intra-articular injection of MSU-induced inflammatory arthritis could result from UA injection [ 57 ].…”