Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis

Gasse, Paméla; Riteau, Nicolas; Pétrilli, Virginie; Tschopp, Jürg; Lagente, Vincent; Quesniaux, Valérie; Ryffel, Bernhard; Couillin, Isabelle

doi:10.1016/s0761-8425(08)75060-5

Cited by 79 publications

(120 citation statements)

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“…Friedman test, p There are relatively scarce data about the involvement of UA in the acute phase of IS although previous studies have highlighted the relationship of UA with the inflammatory process which plays a crucial role during IS (Bandukwala, Huang, Zaltzman, Nash, & Prasad, 2009). UA has been shown to be the endogenous inductor of interleukin-1beta (IL-1β) production in lung inflammation and fibrosis (Gasse et al, 2009). IL-1β together with tumor necrosis factor alpha (TNF-α) is the cytokine which initiates the inflammatory response (for review, see Castillo & Rodriguez, 2004).…”

Section: Resultsmentioning

confidence: 99%

Serum Bilirubin and Uric Acid Levels as the Bad Prognostic Factors in the Ischemic Stroke

Kurzepa

Bielewicz

Stelmasiak

et al. 2009

International Journal of Neuroscience

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Bilirubin (Bil) and uric acid (UA) are the endogenous antioxidant compounds possibly involved in the pathogenesis of ischemic stroke (IS). Our goal was to find the relationship between serum Bil and UA levels with clinical presentation and outcomes of patients suffering from IS. Forty-three patients (mean age: 71.9 years, +/- 12.1; women: 48.8%) with confirmed IS were enrolled. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) after 1, 3, 5, and 10 days and functional disability was assessed three months after stroke onset using the Barthel Index (BI). Serum Bil and UA levels were measured 1, 3, 5, and 10 days after stroke. The difference between NIHSS scores from days 1 and 10 (improvement ratio) inversely correlated with the average UA serum level (r = -0.48, p < .01) but not with the average Bil level. Negative correlations were observed between the BI measured three months after stroke compared to the average Bil serum level (r = -0.5, p < .01). However, no relationship between BI and UA level was observed. Our results indicated that Bil and UA levels are poor prognostic factors for ischemic stroke.

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Section: Resultsmentioning

confidence: 99%

Serum Bilirubin and Uric Acid Levels as the Bad Prognostic Factors in the Ischemic Stroke

Kurzepa

Bielewicz

Stelmasiak

et al. 2009

International Journal of Neuroscience

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“…This was shown for asbestosis via a decrease in the immediate inflammatory cellular influx into the lungs following inhalation of asbestos and for silicosis in impairment in the chronic inflammation and fibrosis associated with inhaled silica crystals. In addition to the study demonstrating the role of the NLRP3 inflammasome in bleomycin-induced lung injury [43], these studies show that NLRP3 plays a central role in mediating a number of pulmonary diseases culminating in pulmonary fibrosis. It will be interesting to expand these studies and determine if other fibrotic diseases are also dependent upon the activity of the NLRP3 inflammasome.…”

Section: Particulate Activators Of the Nlrp3 Inflammasomementioning

confidence: 99%

“…However in this particular context, the role of endogenous molecules such as uric acid or ATP in the activation of the NLRP3 inflammasome have yet to be demonstrated. In a recent study by Gasse and colleagues it was shown that bleomycin-induced pulmonary injury and fibrosis were dependent on the NLRP3 inflammasome [43]. Uric acid released from injured cells played a central role in mediating pulmonary injury and inhibitors of uric acid synthesis, such as allopurinol or uricase, decreased bleomycin-induced pulmonary damage in vivo [43].…”

Section: Particulate Activators Of the Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 inflammasome: A sensor of immune danger signals

Cassel

Joly

Sutterwala

2009

Seminars in Immunology

190

146

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The innate immune system senses danger signals via evolutionary conserved receptors. The nucleotide-binding domain leucine-rich repeat containing receptors (NLR) family is a group of intracellular receptors that drive a wide variety of inflammatory responses. A number of the NLR family members can form inflammasomes, which are multiprotein complexes that can activate caspase-1 and ultimately lead to the processing and secretion of interleukin (IL)-1β, IL-18 and IL-33. One of the best-studied members of the NLR family is NLRP3 for which a number of divergent activators have recently been described. These and other studies examining the NLRP3 inflammasome will be discussed in this review.

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“…It has now been shown that polymorphisms in NLRP1 are associated with SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc patients [24]. Using the bleomycin model of fibrosis they showed that NALP3-knockout mice had significantly reduced fibrosis compared with wild-type mice receiving bleomycin [27]. AIM2 is a intracellular bacterial and a viral DNA sensor [26].…”

Section: Nod-like Receptors and Sscmentioning

confidence: 99%

Innate immunity in systemic sclerosis pathogenesis

O’Reilly¹

2013

Clinical Science

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The innate immune system is a critical part of the response to pathogens and overall immunity. Compared with the adaptive immune response, these innate responses are not antigen-specific and recognize patterns in bacteria, viruses and fungi. Chief among these are TLRs (Toll-like receptors). TLRs are PRRs (pattern recognition receptors) that are germ-line-encoded and are also able to recognize endogenous molecules that are released upon cell damage or stress and have been demonstrated to have a key role in numerous autoimmune diseases, including RA (rheumatoid arthritis) and SSc (systemic sclerosis). SSc is an autoimmune disorder in which vascular injury occurs and there is a chronic low-grade inflammation followed by excessive ECM (extracellular matrix) deposition and ultimately fibrosis. The fibrosis ultimately leads to organ dysfunction and death. The preceding vascular damage and activation of the innate immune system leads to mobilization of the innate lymphoid cells and the up-regulation of multiple genes and pro-fibrotic cytokines. These locally released cytokines activate resident fibroblasts to differentiate into myofibroblasts. The aim of the present review is to explore the role of the innate immune system in SSc and TLRs and how these interact with stromal cells to produce fibrosis. Targeting the innate immune system or specific components of the TLR signalling cascade may be a novel therapeutic option in what is an incurable disease.

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Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis

Cited by 79 publications

References 0 publications

Serum Bilirubin and Uric Acid Levels as the Bad Prognostic Factors in the Ischemic Stroke

Serum Bilirubin and Uric Acid Levels as the Bad Prognostic Factors in the Ischemic Stroke

The NLRP3 inflammasome: A sensor of immune danger signals

Innate immunity in systemic sclerosis pathogenesis

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