title: IL-27 enhances LPS-induced IL-1β in human monocytes and murine macrophages.
abstract: IL-27 bridges innate and adaptive immunity by modulating cytokine production from myeloid cells and regulating Th cell differentiation. During bacterial infection, TLR4 triggering by LPS induces IL-27 production by monocytes and macrophages. We have previously shown that IL-27 can prime monocytes for LPS responsiveness by enhancing TLR4 expression and intracellular signaling. If unregulated, this could result in damaging inflammation, whereas on the other hand, this may also provide greater responses by inflammatory processes induced in response to bacterial pathogens. A key process in fine-tuning inflammatory responses is activation of the inflammasome, which ultimately results in IL-1β production. Herein, we investigated the molecular mechanisms by which IL-27 modulates LPS-induced IL-1β secretion in monocytes and macrophages. We found that when delivered simultaneously with LPS, IL-27 augments activation of caspase-1 and subsequent release of IL-1β. Furthermore, we determined that IL-27 primes cells for enhanced IL-1β production by up-regulating surface expression of TLR4 and P2X purinoceptor 7 (P2X7) for enhanced LPS and ATP signaling, respectively. These findings provide new evidence that IL-27 plays an important role in the proinflammatory capacity of monocytes and macrophages via enhancing IL-1β secretion levels triggered by dual LPS-ATP stimulation.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Carlene
authors.initials: C
authors.lastname: Petes
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wynick
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.|Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA; and.
authors.forename: Christina
authors.initials: C
authors.lastname: Guzzo
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Divya
authors.initials: D
authors.lastname: Mehta
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Logan
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Banfield
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Sameh
authors.initials: S
authors.lastname: Basta
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cooper
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; kgee@queensu.ca.
authors.forename: Katrina
authors.initials: K
authors.lastname: Gee
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000276:immunology
chemical_list: C508585:IL1B protein, human; C587672:IL1B protein, mouse; C486767:Il27 protein, mouse; D053583:Interleukin-1beta; D007378:Interleukins; D008070:Lipopolysaccharides; C464565:MYDGF protein, human; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000255:Adenosine Triphosphate; D020170:Caspase 1
keywords: Toll-like receptor; inflammasome; inflammation; innate immunity; lipopolysaccharide