title: The E3 ubiquitin ligase RNF144B is LPS-inducible in human, but not mouse, macrophages and promotes inducible IL-1β expression.
abstract: Differences in human and mouse immune responses may partly reflect species-specific adaptations and can provide important insights into human immunity. In this study, we show that RNF144B, which encodes an E3 ubiquitin ligase, was lipopolysaccharide-inducible in primary human macrophages and in human macrophage-like THP-1 cells. In contrast, Rnf144b was not lipopolysaccharide-inducible in several mouse cell populations, including primary macrophages from C57BL/6 and BALB/c mice and RAW264.7 macrophages. Similarly, Rnf144b was not up-regulated by infection of C57BL/6 mice with Escherichia coli Although the human and mouse RNF144B genes have conserved transcription start sites, cap analysis of gene expression data confirmed that the RNF144B promoter directs transcription in human but not mouse macrophages. The human and mouse RNF144B genes are controlled by highly conserved TATA-containing promoters, but subtle differences in transcription factor binding sites may account for differential regulation. Using gene silencing, we showed that RNF144B is necessary for priming of inflammasome responses in primary human macrophages. Specifically, RNF144B promotes lipopolysaccharide-inducible IL-1b mRNA expression but does not regulate expression of several other lipopolysaccharide-inducible cytokines (e.g., interleukin-10, interferon-γ) or affect expression of inflammasome components or substrates (e.g., procaspase-1, pro-interleukin-18). Our findings thus revealed a species-specific regulatory mechanism for selective inflammasome priming in human macrophages.
authors.affiliation: Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland, Australia; IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and.
authors.forename: Juliana K
authors.initials: JK
authors.lastname: Ariffin
authors.affiliation: Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland, Australia; IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and.
authors.forename: Ronan
authors.initials: R
authors.lastname: Kapetanovic
authors.affiliation: Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland, Australia; IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and.
authors.forename: Kolja
authors.initials: K
authors.lastname: Schaale
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Marcela
authors.initials: M
authors.lastname: Gatica-Andrades
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Antje
authors.initials: A
authors.lastname: Blumenthal
authors.affiliation: Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland, Australia; IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and.
authors.forename: Kate
authors.initials: K
authors.lastname: Schroder
authors.affiliation: Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland, Australia; IMB Centre for Inflammation and Disease Research, The University of Queensland, Brisbane, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; and m.sweet@imb.uq.edu.au.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sweet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C000607305:RNF145 protein, mouse; C508914:RNF144B protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Toll-like receptor; gene expression; inflammasome; inflammation; species differences