Stimulation of inducible nitric oxide synthase by monosodium urate crystals in macrophages and expression of iNOS in gouty arthritis

Chen, Linda; Hsieh, Mao Chih; Ho, Hsin Chiu; Liu, Yung Hung; Chou, Der Tsay; Tsai, Shin-Han

doi:10.1016/j.niox.2004.09.003

Cited by 41 publications

(49 citation statements)

References 42 publications

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“…Chen et al [45] have demonstrated that iNOS protein and mRNA expressions are upregulated in response to MSU stimulation in vitro monocytes/macrophages. Particularly, the role of PI3K/Akt, JAK/STAT, NF-kB, and ERK1/2 signaling pathways has been established in the induction of iNOS expression by MSU [46] (Fig. 2).…”

Section: Oxidative Stress Mechanisms In Goutmentioning

confidence: 97%

Molecular basis of oxidative stress in gouty arthropathy

et al. 2015

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Gout is a disorder of urate metabolism in which persistent high urate levels in the extracellular fluids result in the deposition of monosodium urate (MSU) crystal in joints and periarticular tissues. In recent years, this disease represents an increasingly common health problem, so the pace of investigation in the field has accelerated tremendously. New research advances in the pathogenesis of hyperuricemia and in the understanding of how MSU crystals induce an acute gouty attack have been focused in this review on the processes of inflammation and involvement of the innate immune response; in addition, we discuss new knowledge about the role of the reactive oxygen species in establishing oxidative stress in MSU crystal-induced arthritis.

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Section: Oxidative Stress Mechanisms In Goutmentioning

confidence: 97%

Molecular basis of oxidative stress in gouty arthropathy

et al. 2015

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“…MSU crystals are also taken up by these cells via phagocytosis, followed by lysosomal fusion, oxidative burst and synthesis of nitric oxide, and the release of inflammatory mediators [36,37]. Crystal uptake disrupts the phagolysosome acidic compartment and leads to the release of cathepsin B [38].…”

Section: Local Situation In Goutmentioning

confidence: 99%

How neutrophil extracellular traps orchestrate the local immune response in gout

et al. 2015

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Neutrophil granulocytes possess a large arsenal of pro-inflammatory substances and mechanisms that empower them to drive local acute immune reactions to invading microorganisms or endogenous inflammatory triggers. The use of this armory needs to be tightly controlled to avoid chronic inflammation and collateral tissue damage. In gout, inflammation arises from precipitation of uric acid in the form of needle-shaped monosodium urate crystals. Inflammasome activation by these crystals in local immune cells results in a rapid and dramatic recruitment of neutrophils. This neutrophil influx is accompanied by the infamously intense clinical symptoms of inflammation during an acute gout attack. Neutrophilic inflammation however is equipped with a built-in safeguard; activated neutrophils form neutrophil extracellular traps (NETs). At the very high neutrophil densities that occur at the site of inflammation, NETs build aggregates that densely pack the monosodium urate (MSU) crystals and trap and degrade pro-inflammatory mediators by inherent proteases. Local removal of cytokines and chemokines by aggregated NETs explains how acute inflammation can stop in the consistent presence of the inflammatory trigger. Aggregated NETs resemble early stages of the typical large MSU deposits that constitute the pathognomonic structures of gout, tophi. Although tophi contribute to muscosceletal damage and mortality in patients with chronic gout, they can therefore be considered as a payoff that is necessary to silence the intense inflammatory response during acute gout.

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“…Alternatively, it has been suggested that extracellular MSU crystals activate complement (5)(6)(7)(8)(9) and other extracellular enzymes such as bradykinin and kallikrein and thereby generate proinflammatory mediators (10). Yet another potential mechanism is that phagocytosis of MSU crystals may stimulate the production of eicosanoids and reactive oxygen species (11)(12)(13) as well as proinflammatory cytokines (e.g., TNF-a [ref. 14], IL-1b [ref.…”

Section: Introductionmentioning

confidence: 99%

MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals

Chen¹

2006

Journal of Clinical Investigation

427

385

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While it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1-11 to activate NF-kB. In contrast, mice deficient in the MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 production and IL-1R activation play essential roles in MSU-triggered inflammation. IL-1R deficiency in bone marrow-derived cells did not affect the inflammatory response; however, it was required in nonbone marrow-derived cells. These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway.

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Stimulation of inducible nitric oxide synthase by monosodium urate crystals in macrophages and expression of iNOS in gouty arthritis

Cited by 41 publications

References 42 publications

Molecular basis of oxidative stress in gouty arthropathy

Molecular basis of oxidative stress in gouty arthropathy

How neutrophil extracellular traps orchestrate the local immune response in gout

MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals

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