TLR2 and TLR4 mediate an activation of adipose tissue renin-angiotensin system induced by uric acid

Zhang, Junxia; Diao, Bo; Lin, Xue; Xu, Jianrong; Tang, Feng

doi:10.1016/j.biochi.2019.04.013

Cited by 22 publications

(24 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this regard, a previous work reported that the risk of gout-a pathology known by deposition of monosodium urate crystals in joints-is directly associated with the polymorphism rs2149356 related to high TLR4 production [35]. Likewise, a very recent study demonstrated that uric acid promotes the mRNA expression of TLR4 in rat adipocytes in vitro [36]. Thus, we speculate that uric acid is able to induce TNF-alpha production via TLR4 activation, a phenomenon that provides proinflammatory features to human macrophages.…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 97%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Experimental studies on human cell cultures and hyperuricemic animal models have shown that UA can upregulate the renin-angiotensin-aldosterone system (RAAS) [21][22][23][24][25][26]. In addition, RAAS can be indirectly activated by UA-mediated inflammatory status [23,69].…”

Section: Biology Of the Association Between Ua And Hypertensionmentioning

confidence: 99%

“…However, the exact mechanism whereby UA can induce arteriolopathy remains partially unsolved. UA-induced oxidative stress and inflammation may play a role, being responsible for the pathogenesis of endothelial dysfunction [24][25][26]32,33]. Another possible cause of afferent arteriolopathy is the UA-mediated vascular smooth muscle cell proliferation [25,31,77,78].…”

Section: Biology Of the Association Between Ua And Hypertensionmentioning

confidence: 99%

“…Since then, numerous studies have confirmed this strong association [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Several mechanisms have been proposed to explain the potential role of SUA in the development of hypertension, including UA-mediated kidney afferent arteriolopathy, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, inflammation, and endothelial dysfunction [21][22][23][24][25][26][27][28][29][30][31][32][33]. However, the precise pathophysiologic patterns remain elusive.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Uric Acid and Hypertension: Prognostic Role and Guide for Treatment

Piani

Cicero

Borghi

2021

JCM

View full text Add to dashboard Cite

The relationship between serum uric acid (SUA) and hypertension has been a subject of increasing interest since the 1870 discovery by Frederick Akbar Mahomed. Several epidemiological studies have shown a strong association between high SUA levels and the presence or the development of hypertension. Genetic analyses have found that xanthine oxidoreductase (XOR) genetic polymorphisms are associated with hypertension. However, genetic studies on urate transporters and Mendelian randomization studies failed to demonstrate a causal relationship between SUA and hypertension. Results from clinical trials on the role of urate-lowering therapy in the management of patients with hypertension are not uniform. Our study sought to analyze the prognostic and therapeutic role of SUA in the hypertensive disease, from uric acid (UA) biology to clinical trials on urate-lowering therapies.

show abstract

“…The vascular remodeling is certainly a key player for the development of arteriolosclerosis [89,90] . Recent studies have shown serum UA as an independent risk factor for the presence of arteriolar hyalinosis and intimal thickening of the vessel analyzed in kidney biopsies [91,92] . Moreover, Sánchez-Lozada et al [69] found that raising the serum UA level could induce oxidative stress with endothelial dysfunction, resulting in the development of both systemic and glomerular hypertension, as well as elevated renal vascular resistance and reduced renal blood flow in turn a powerful activator of RAS.…”

Section: Ras Activation and Atherosclerosismentioning

confidence: 99%

The role of uric acid in renal damage - A history of inflammatory pathways and vascular remodeling

Russo¹,

Verzola²,

Cappadona³

et al. 2021

View full text Add to dashboard Cite

The association of hyperuricemia with cardiovascular risk, hypertension, atherosclerosis, metabolic syndrome, mortality, and chronic kidney disease has been largely described in clinical studies. Several pathogenetic mechanisms explaining uric acid mediated renal damage have been hypothesized, including crystal deposition, oxidative stress, arteriolosclerosis, and glomerular hypertension. Currently, two explanations for hyperuricemiainduced renal injury are the most widely accepted. Firstly, the fact that uric acid is recognized by receptors involved in the innate immune response as a dangerous molecule appears to be a powerful trigger for the inflammatory cascade, which ultimately lead to renal fibrosis. Secondly, serum uric acid has been demonstrated to be implicated in the renin-angiotensin system activation and nitric oxide synthesis inhibition, which promote endothelial dysfunction and proliferation of vascular smooth muscle cells, resulting in glomerulosclerosis and interstitial fibrosis. In this review, we focus on experimental data demonstrating pathophysiological mechanisms linking uric acid to inflammation and oxidative stress, which contribute to the development and progression of renal injury. In addition, we describe endothelial and vascular dysfunction crucial playmakers in kidney impairment induced by uric acid.

show abstract

TLR2 and TLR4 mediate an activation of adipose tissue renin-angiotensin system induced by uric acid

Cited by 22 publications

References 26 publications

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

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

Uric Acid and Hypertension: Prognostic Role and Guide for Treatment

The role of uric acid in renal damage - A history of inflammatory pathways and vascular remodeling

Contact Info

Product

Resources

About