Expression and regulation of interleukin-33 in human monocytes

Christopher J. Nile, Emma Barksby, Paiboon Jitprasertwong, Philip M. Preshaw, John J. Taylor (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

Interleukin-33 (IL-33) is an IL-1 family cytokine that has a role in regulating T helper type 2 cytokines and mast cell development. Expression of IL-33 is also associated with chronic inflammatory conditions such as rheumatoid arthritis. However, there is little information regarding IL-33 in myeloid cell immune responses, which are important in immunity and inflammation. We therefore investigated the expression, intracellular location and regulation of myeloid cell IL-33 by lipopolysaccharide (LPS) from Escherichia coli and the periodontal pathogen Porphyromonas gingivalis. We detected IL-33 messenger RNA in the human promonocytic cell line THP-1, in monocytes derived from these cells and in primary human monocytes. However, IL-33 was not expressed in primary monocyte-derived dendritic cells. Stimulation of monocytes with E. coli LPS (Toll-like receptor 4 agonist) and LPS from P. gingivalis (Toll-like receptor 2 agonist) up-regulated IL-33 at both the messenger RNA and protein levels but IL-1β and tumour necrosis factor-α had no effect. The IL-33 protein was mainly found in the cytoplasm of monocytes with no evidence of nuclear translocation in stimulated cells. Furthermore, no IL-33 secretion was detected after stimulation with LPS and/or ATP. These data indicate that the function, if any, of IL-33 in activated monocytes is primarily intracellular. Interestingly, immunofluorescence analysis indicated that IL-33 was sequestered in the nucleus of monocytes undergoing apoptosis but released into the extracellular milieu by LPS-stimulated cells in which necrosis had been induced by freeze-thawing. Therefore, this endorses the view that IL-33 may function as an 'alarmin' and have a role in signalling cellular damage and inflammatory disease pathogenesis through release from damaged or necrotic cells.

Original languageEnglish
Pages (from-to)172-180
Number of pages9
JournalImmunology
Volume130
Issue number2
Early online date11 Jan 2010
DOIs
Publication statusPublished - 7 May 2010

Keywords

  • Cytokines
  • Interleukin-1 family
  • Monocytes
  • Myeloid immune cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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