Dysregulation of the NLRP3 inflammasome complex and related cytokines in patients with multiple myeloma

Hematology. 2016 Apr;21(3):144-51. doi: 10.1179/1607845415Y.0000000029. Epub 2015 Jul 6.

Abstract

Objective: The NLRP3 inflammasome complex, an important regulatory factor of inflammation and cell apoptosis, has attracted considerable attention in the development of tumor. Here, we analyzed the expression and clinical significance of NLRP3 inflammasome complex and related cytokines in patients with multiple myeloma (MM).

Methods: Peripheral blood and bone marrow of 38 newly diagnosed myeloma patients and 25 age- and gender-matched healthy people were studied. NLRP3 and caspase-1 were analyzed using quantitative real-time polymerase chain reaction and Western blot and IL-1beta, IL-18, RANKL, and OPG were evaluated by enzyme-linked immunosorbent assay.

Results: We showed that aberrant NLRP3 and caspase-1 expression were observed in MM and down-regulated compared with the healthy people. We further demonstrated that NLRP3 mRNA was negatively correlated with beta2-microglobulin and plasma cell percentage in MM. The downstream cytokines IL-18 and sRANKL/OPG in MM patients were higher than that in control group. Moreover, the lower mRNA levels of NLRP3 and caspase-1 were shown to be positively correlated with IL-1beta in newly diagnosed MM patients.

Conclusions: This study demonstrated that dysregulated expression of NLRP3-caspase-1-IL-1beta axis was observed in patients with MM, suggesting they might be involved in the pathogenesis of MM.

Keywords: Caspase-1; IL-1beta; Multiple myeloma; NLRP3 inflammasome.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Caspase 1 / biosynthesis*
  • Cytokines / biosynthesis*
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Inflammasomes / biosynthesis*
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • NLR Family, Pyrin Domain-Containing 3 Protein / biosynthesis*
  • Neoplasm Proteins / biosynthesis*

Substances

  • Cytokines
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Neoplasm Proteins
  • Caspase 1