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Expression and regulation of interleukin-33 in human monocytes

Lookup NU author(s): Dr Christopher NileORCiD, Paiboon Jitprasertwong, Professor Philip Preshaw, Dr John TaylorORCiD

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Abstract

P>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-1 beta and tumour necrosis factor-alpha 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.


Publication metadata

Author(s): Nile CJ, Barksby E, Jitprasertwong P, Preshaw PM, Taylor JJ

Publication type: Article

Publication status: Published

Journal: Immunology

Year: 2010

Volume: 130

Issue: 2

Pages: 172-180

Print publication date: 11/01/2010

ISSN (print): 0019-2805

ISSN (electronic): 1365-2567

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1365-2567.2009.03221.x

DOI: 10.1111/j.1365-2567.2009.03221.x


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Funding

Funder referenceFunder name
Newcastle Healthcare charity
DHCS/03/G121/46UK Department of Health

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