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

Overview of attention for article published in Arthritis Research & Therapy, September 2015
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84 Mendeley
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Title
Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis
Published in
Arthritis Research & Therapy, September 2015
DOI 10.1186/s13075-015-0775-2
Pubmed ID
Authors

Christianna Choulaki, Garyfallia Papadaki, Argyro Repa, Eleni Kampouraki, Konstantinos Kambas, Konstantinos Ritis, George Bertsias, Dimitrios T. Boumpas, Prodromos Sidiropoulos

Abstract

Interleukin-1β (IL-1β) is a major inflammatory cytokine, produced predominantly by innate immune cells through NLRP3-inflammasome activation. Both intrinsic and extrinsic danger signals may activate NLRP3. Genetic variations in NLRP3-inflammasome components have been reported to influence rheumatoid arthritis (RA) susceptibility and severity. We sought to assess the activity of NLRP3-inflammasome in patients with active RA compared to healthy individuals. Intracellular protein expression of NLRP3, ASC, pro- and active caspase-1, pro- and active IL-1β was assessed by immunoblotting both at baseline and upon inflammasome activation. NLRP3 function (IL-1β secretion) was assessed upon priming of TLR2 (Pam(3)CysSK(4), TLR3 (poly(I:C)) or TLR4 (LPS) and ATP sequential treatment. We used caspase inhibitors (casp-1, 3/7 and 8) to assess their contribution to IL-1β maturation. All experiments were performed in whole blood cells. Active RA patients (n = 11) expressed higher basal intracellular levels of NLRP3 (p < 0.008), ASC (p < 0.003), active caspase-1 (p < 0.02) and pro-IL-1β (p < 0.001). Upon priming with TLR4 (LPS) and ATP, RA-derived cell extracts (n = 7) displayed increased expression of NLRP3 (p < 0.01) and active caspase-1 (p < 0.001). Secreted IL-1β in culture supernatants from whole blood cells activated with TLR4 (LPS) or TLR3 agonist (poly(I:C)) plus ATP was higher in RA patients (n = 20) versus controls (n = 18) (p < 0.02 for both). Caspase-1 inhibition significantly reduced IL-1β secretion induced by all stimuli, whereas caspase-8 inhibition affected only TLR4 and TLR3 cell priming. Patients with active RA have increased expression of NLRP3 and NLRP3-mediated IL-1β secretion in whole blood cells upon stimulation via TLR3 and TLR4 but not TLR2. In these patients, IL-1β secretion seems to be predominately driven by caspase-1 and caspase-8. Targeting NLRP3 or downstream caspases may be of benefit in suppressing IL-1β production in RA.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Unknown 83 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 24%
Researcher 13 15%
Student > Bachelor 11 13%
Student > Master 8 10%
Student > Doctoral Student 4 5%
Other 11 13%
Unknown 17 20%
Readers by discipline Count As %
Medicine and Dentistry 18 21%
Agricultural and Biological Sciences 12 14%
Immunology and Microbiology 12 14%
Biochemistry, Genetics and Molecular Biology 8 10%
Pharmacology, Toxicology and Pharmaceutical Science 6 7%
Other 9 11%
Unknown 19 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 June 2021.
All research outputs
#13,880,571
of 21,392,919 outputs
Outputs from Arthritis Research & Therapy
#1,997
of 2,833 outputs
Outputs of similar age
#142,727
of 263,675 outputs
Outputs of similar age from Arthritis Research & Therapy
#1
of 1 outputs
Altmetric has tracked 21,392,919 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,833 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,675 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them