Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis

Choulaki, Christianna; Papadaki, Garyfalia; Repa, Argyro; Kampouraki, Eleni; Kambas, Konstantinos; Ritis, Konstantinos; Βertsias, George; Boumpas, Dimitrios T.; Sidiropoulos, Prodromos

doi:10.1186/s13075-015-0775-2

Cited by 152 publications

(99 citation statements)

References 48 publications

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“…Inflammasome activation TLR-4 stimulation with lipopolysaccharide (LPS, Escherichia coli O111; Merck) (250 pg·mL −1 , incubated for 2 h at a 37°C/5% CO 2 humidified incubator) was followed by NLRP3 inflammasome activation with a 5 mM ATP pulse (ATP disodium salt hydrate; Sigma-Aldrich) for 20 min at 37°C/5% CO 2 , in the presence or absence of caspase-1 inhibitor (Calbiochem) (online supplementary figure S1), as previously described [24]. Cells were harvested by centrifugation at 1500×g at 4°C.…”

Section: Methodsmentioning

confidence: 99%

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

et al. 2016

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In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1β and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1β and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1β were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1β and partly IL-18 secretion, in contrast to controls, which showed robust IL-1β and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1β, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1β levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1β suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis. @ERSpublications Distinct NLRP3 inflammasome activation profiles between autoimmune and IPF lung macrophages compared with controls

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Section: Methodsmentioning

confidence: 99%

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

et al. 2016

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“…[21][22][23] In addition, previous studies showed that the NLRP3 inflammasome complex and cytokines IL-1b and IL-18 play essential roles in the development of T2DM and its major complica- . Data represent means 6 SD.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Expression of NLRP3 Inflammasome-Related Inflammation in Diabetic Retinopathy

Chen

Zhang

Liao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The aim of this study was to determine the association between nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation and disease severity in diabetic retinopathy (DR).METHODS. Blood samples were collected from 64 patients with diabetes (DR, 43; without DR, 21) and 25 healthy controls. The protein and mRNA expression levels of NLRP3 inflammasomes in peripheral blood mononuclear cells were determined using western blotting and quantitative real-time reverse transcription-PCR. A total of 82 vitreous samples were obtained from patients with DR (n ¼ 60) and nondiabetic controls (n ¼ 22). All patients were candidates for vitrectomy. Interleukin (IL)-1b and IL-18 in the peripheral blood mononuclear cell culture medium and vitreous fluid were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining for apoptosis-associated specklike protein with a caspase recruitment domain (ASC) and NLRP3 was performed in fibrovascular membranes from 21 proliferative DR patients and 22 controls with idiopathic epiretinal membranes. RESULTS.We observed increased gene and protein expression of NLRP3, ASC, and caspase-1 in peripheral blood mononuclear cells of adults with DR compared with that in normal controls. Furthermore, the elevated expressions of NLRP3 and ASC were observed in the fibrovascular membranes from 21 adults with proliferative DR when compared with the 22 controls. IL-1b and IL-18 in the peripheral blood mononuclear cells and vitreous fluid were elevated in the DR patients when compared with controls.CONCLUSIONS. These outcomes suggested that NLRP3 inflammasomes are upregulated in adults with DR and may play a key role in the pathogenesis and progression of DR.

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“…Targeting NALP3 or downstream caspases may be of benefit in suppressing IL-1b production in RA. 126 Other investigators demonstrated that A20, an RA susceptibility gene, puts a break in NALP3 and reduces inflammasome activation. 125 Likewise, excessive NALP3 inflammasome activation drives arthritis in A20 knockout mice, suggesting that A20 mutant mice might be a suitable preclinical model for validating the effectiveness of experimental therapies for RA-targeting inflammasomes, IL-1 signalling, or both.…”

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confidence: 99%

The inflammasome as a target for pain therapy

Zhang¹,

Li²,

Li³

et al. 2016

British Journal of Anaesthesia

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The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades. Therefore, it has been proposed that targeting inflammasome activity may be a novel and effective therapeutic strategy for these pain-related diseases. The purpose of this narrative review article is to provide the reader with an overview of the activation and regulation of inflammasomes and to investigate the potential therapeutic role of inflammasome inhibition in the treatment of diseases characterized by pain, including the following: complex regional pain syndrome, gout, rheumatoid arthritis, inflammatory pain, neuropathic pain, chronic prostatitis, chronic pelvic pain syndrome, and fibromyalgia. We conclude that the role of the inflammasome in pain-associated diseases is likely to be inflammasome subtype and disease specific. The currently available evidence suggests that disease-specific targeting of the assembly and activity of the inflammasome complex may be a novel therapeutic opportunity for the treatment of refractory pain in many settings.

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Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis

Cited by 152 publications

References 48 publications

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

Enhanced Expression of NLRP3 Inflammasome-Related Inflammation in Diabetic Retinopathy

The inflammasome as a target for pain therapy

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