title: Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47phox.
abstract: Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47phox, a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47phoxupon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Bharatwaj
authors.initials: B
authors.lastname: Sowrirajan
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Poudyal
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sui
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20802, USA.
authors.forename: Suk See
authors.initials: SS
authors.lastname: DeRavin
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Sato
authors.affiliation: Neutrophil Monitoring Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kuhns
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Noguchi
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20802, USA.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Imamichi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D019255:NADPH Oxidases / Q000235:genetics* / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000276:immunology; D013481:Superoxides / Q000276:immunology / Q000378:metabolism*
chemical_list: C508598:IL4 protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D013481:Superoxides; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1