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

• Published in: Arthritis research & therapy 2015-09, Vol.17 (1), p.257-257, Article 257
• Main Authors: Choulaki, Christianna, Papadaki, Garyfallia, Repa, Argyro, Kampouraki, Eleni, Kambas, Konstantinos, Ritis, Konstantinos, Bertsias, George, Boumpas, Dimitrios T, Sidiropoulos, Prodromos
• Format: Article
• Language: English
• Subjects: Analysis; Arthritis; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - immunology; Blotting, Western; Care and treatment; Carrier Proteins - blood; Carrier Proteins - immunology; Complications and side effects; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammasomes - blood; Inflammasomes - immunology; Leukocytes - immunology; Male; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Rheumatoid factor; Risk factors
• ISSN: 1478-6354; 1478-6362; 1478-6354
• DOI: 10.1186/s13075-015-0775-2

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