title: Stimulation of inflammatory gene expression in human preadipocytes by macrophage-conditioned medium: upregulation of IL-6 production by macrophage-derived IL-1β.
abstract: The aim of this study was to examine the effects of macrophage secretions on global gene expression in human preadipocytes using microarrays. Preadipocytes were cultured with unconditioned or conditioned medium from U937 macrophages, and gene expression examined with Agilent arrays (43,000 probes). 472 transcripts were differentially regulated (>2-fold difference; P<0.05) between preadipocytes in the conditioned medium compared to the unconditioned; 401 were upregulated and 71 downregulated. The upregulated transcripts were particularly linked to inflammation, including IL-1β, IL-6, and CCL20 (16.8-, 10.0-, and 8.9-fold increases, respectively) together with matrix metalloproteinases (MMP3, MMP9 and MMP12). Major pathways regulated by the conditioned medium were linked to inflammation, macrophage infiltration and lipid accumulation. Network analysis identified NFkB and IL-1β as central nodes in the upregulation of multiple inflammation-related genes. Treatment with an IL-1β neutralising antibody abolished the stimulation of IL-6 secretion by conditioned medium, indicating that IL-1β is a key regulator of preadipocyte IL-6 production. Macrophages evoke extensive changes in preadipocyte gene expression.
authors.affiliation: Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: O'Hara
authors.forename: Fei-Ling
authors.initials: FL
authors.lastname: Lim
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Mazzatti
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000276:immunology; D016328:NF-kappa B / Q000096:biosynthesis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D057134:Antibodies, Neutralizing; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D020782:Matrix Metalloproteinases