title: IFN-γ-induced IL-27 and IL-27p28 expression are differentially regulated through JNK MAPK and PI3K pathways independent of Jak/STAT in human monocytic cells.
abstract: IL-27, a member of the IL-12 cytokine family, is a key immunoregulatory cytokine produced predominantly by monocytic cells and mediates innate and adaptive immune responses. IL-27 has been shown to be produced by human monocytic cells primed with IFN-γ and in response to a second stimulus such as LPS. In this study, we show for the first time that IFN-γ alone without any second stimulus can induce IL-27p28 gene expression and IL-27 protein production by human monocytic cells. The signaling pathways that govern IL-27 production in general, and particularly following stimulation of monocytic cells with IFN-γ are not known. We investigated the signaling pathways governing the regulation of IL-27 protein and its subunit IL-27p28 following stimulation with IFN-γ in primary human monocytic cells. Our results suggest that IFN-γ-mediated IL-27 protein but not IL-27p28 gene expression is positively regulated by the C-Jun N-terminal kinases (JNK), mitogen-activated protein kinases (MAPKs) and the phosphoinositide 3-kinase (PI3K), independent of the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) signaling in primary human monocytes.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: mblah011@uottawa.ca.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blahoianu
authors.forename: Ali A R
authors.initials: AA
authors.lastname: Rahimi
authors.forename: Maya
authors.initials: M
authors.lastname: Kozlowski
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Angel
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D064094:Interleukin-27 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D002867:Chromones; D004791:Enzyme Inhibitors; D007371:Interferon-gamma; D064094:Interleukin-27; D048031:JNK Mitogen-Activated Protein Kinases; D053612:Janus Kinases; D008070:Lipopolysaccharides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050791:STAT Transcription Factors; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: IFN-γ; IL-27; Jak/STAT; MAPK; PI3K