Expression and regulation of interleukin-33 in human monocytes

Nile, C.J. , Barksby, E., Jitprasertwong, P., Preshaw, P.M. and Taylor, J.J. (2010) Expression and regulation of interleukin-33 in human monocytes. Immunology, 130(2), pp. 172-180. (doi: 10.1111/j.1365-2567.2009.03221.x)

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 necroti

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nile, Dr Christopher
• Authors: Nile, C.J., Barksby, E., Jitprasertwong, P., Preshaw, P.M., and Taylor, J.J.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Immunology
• Publisher: Blackwell
• ISSN: 0019-2805
• ISSN (Online): 1365-2567
• Published Online: 11 January 2010