Deregulated NLRP3 and NLRP1 inflammasomes and their correlations with disease activity in systemic lupus erythematosus

J Rheumatol. 2014 Mar;41(3):444-52. doi: 10.3899/jrheum.130310. Epub 2013 Dec 15.

Abstract

Objective: NOD-like receptor family, pyrin domain containing 3 and 1 (NLRP3 and NLRP1) inflammasomes are molecular platforms that sense the damage or danger signals of cells. We investigated whether NLRP3/NLRP1 inflammasomes are involved in the pathogenesis and progression of systemic lupus erythematosus (SLE).

Methods: Expressions of inflammasome components at the mRNA and protein levels in the peripheral blood mononuclear cells (PBMC) from patients with SLE and healthy controls were investigated by quantitative real-time transcription PCR and Western blot, respectively. Correlations between NLRP3/NLRP1 inflammasome components' expression and clinical disease progression were investigated. Expressions of NLRP3/NLRP1 inflammasomes before and after treatment in the patients with SLE were also analyzed and compared.

Results: Our data showed that expressions of NLRP3/NLRP1 inflammasomes were significantly downregulated in PBMC from patients with SLE compared with PBMC from healthy controls. Further, expressions of NLRP3/NLRP1 inflammasomes were negatively correlated with the SLE Disease Activity Index, and regular glucocorticoid treatment significantly corrected this deregulation of these inflammasomes. Further analysis showed that type I interferon (IFN) level was significantly negatively correlated with expression of NLRP3/NLRP1 inflammasomes, which indicated that enhanced IFN-I level in patients with SLE was responsible, at least to a great degree, for the deregulation of inflammasomes.

Conclusion: These results indicated deregulation of NLRP3/NLRP1 inflammasomes in patients with SLE, and suggested an important role for inflammasomes in the pathogenesis and progression of SLE.

Keywords: AUTOIMMUNE DISEASE; DISEASE ACTIVITY; INFLAMMATION; SYSTEMIC LUPUS ERYTHEMATOSUS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adolescent
  • Adult
  • Apoptosis Regulatory Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Disease Progression
  • Female
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Humans
  • Inflammasomes / metabolism*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lupus Vasculitis, Central Nervous System / drug therapy
  • Lupus Vasculitis, Central Nervous System / metabolism*
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLR Proteins
  • Severity of Illness Index
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Glucocorticoids
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLR Proteins
  • NLRP1 protein, human
  • NLRP3 protein, human