Expression and regulation of interleukin-33 in human monocytes.
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-1beta 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.
Nile
Christopher J
CJ
Periodontal Immunobiology Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Barksby
Emma
E
Jitprasertwong
Paiboon
P
Preshaw
Philip M
PM
Taylor
John J
JJ
D021581:Active Transport, Cell Nucleus; D000255:Adenosine Triphosphate / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
C506536:IL33 protein, human; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate