TNF-α potentiates uric acid-induced interleukin-1β (IL-1β) secretion in human neutrophils

Mod Rheumatol. 2018 May;28(3):513-517. doi: 10.1080/14397595.2017.1369924. Epub 2017 Sep 14.

Abstract

Objective: Monosodium urate (MSU) has been shown to promote interleukin-1β (IL-1β) secretion in human monocytes, but the priming signals for NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway remains elusive. In this study, we investigated the role of Tumor necrosis factor-alpha (TNF-α) on MSU-mediated IL-1β induction in human neutrophils.

Methods: Human neutrophils were stimulated with MSU, in the presence or absence of TNF-α priming. The cellular supernatants were analyzed for IL-1β, IL-18, and caspase-1 by enzyme-linked immunosorbent assay (ELISA) methods. Pro-IL-1β mRNA expressions in human neutrophils were analyzed by real-time PCR method.

Results: TNF-α stimulation induced pro-IL-1β mRNA expression; however, MSU stimulation did not induce pro-IL-1β mRNA expression in human neutrophils. TNF-α alone or MSU stimulation did not result in efficient IL-1β secretion in human neutrophils, whereas in TNF-α-primed neutrophils, MSU stimulation resulted in a marked IL-1β and IL-18 secretion. TNF-α-primed neutrophils secreted cleaved caspase-1 (p20), in response to MSU stimulation.

Conclusion: Our data demonstrate that priming of human neutrophils with TNF-α promotes uric acid-mediated IL-1β secretion in the absence of microbial stimulation. These findings provide insights into the neutrophils-mediated inflammatory processes in gouty arthritis.

Keywords: Caspase-1; IL-1β; TNF-α; gout; inflammasome; monosodium urate.

MeSH terms

  • Arthritis, Gouty / metabolism
  • Cells, Cultured
  • Humans
  • Interleukin-1beta / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Uric Acid / pharmacology*

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Uric Acid