title: Endothelial IL-33 Expression Is Augmented by Adenoviral Activation of the DNA Damage Machinery.
abstract: IL-33, required for viral clearance by cytotoxic T cells, is generally expressed in vascular endothelial cells in healthy human tissues. We discovered that endothelial IL-33 expression was stimulated as a response to adenoviral transduction. This response was dependent on MRE11, a sensor of DNA damage that can also be activated by adenoviral DNA, and on IRF1, a transcriptional regulator of cellular responses to viral invasion and DNA damage. Accordingly, we observed that endothelial cells responded to adenoviral DNA by phosphorylation of ATM and CHK2 and that depletion or inhibition of MRE11, but not depletion of ATM, abrogated IL-33 stimulation. In conclusion, we show that adenoviral transduction stimulates IL-33 expression in endothelial cells in a manner that is dependent on the DNA-binding protein MRE11 and the antiviral factor IRF1 but not on downstream DNA damage response signaling.
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.|Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Tor Espen
authors.identifier: 0000-0003-1554-4775
authors.initials: TE
authors.lastname: Stav-Noraas
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.|Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Reidunn J
authors.identifier: 0000-0001-9077-164X
authors.initials: RJ
authors.lastname: Edelmann
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.|Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Lars La Cour
authors.identifier: 0000-0002-7266-3108
authors.initials: LC
authors.lastname: Poulsen
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.|Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Olav
authors.identifier: 0000-0002-4930-3227
authors.initials: O
authors.lastname: Sundnes
authors.affiliation: Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Danh
authors.identifier: 0000-0001-8725-1563
authors.initials: D
authors.lastname: Phung
authors.affiliation: Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Axel M
authors.identifier: 0000-0003-4512-1079
authors.initials: AM
authors.lastname: Küchler
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway; and.
authors.forename: Fredrik
authors.identifier: 0000-0003-0812-0640
authors.initials: F
authors.lastname: Müller
authors.affiliation: Department of Bioengineering, McGill University, Montreal, Quebec H3A OC3, Canada.
authors.forename: Amine A
authors.identifier: 0000-0001-9110-8815
authors.initials: AA
authors.lastname: Kamen
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway; gharalds@rr-research.no.|Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haraldsen
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway; and.
authors.forename: Mari
authors.initials: M
authors.lastname: Kaarbø
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.|Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway.
authors.forename: Johanna
authors.identifier: 0000-0001-5837-5006
authors.initials: J
authors.lastname: Hol
mesh_terms: D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000276:immunology* / Q000378:metabolism; D004249:DNA Damage / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D050856:Interferon Regulatory Factor-1 / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000096:biosynthesis / Q000276:immunology*; D000076228:MRE11 Homologue Protein; D016133:Polymerase Chain Reaction; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C506536:IL33 protein, human; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D000067596:Interleukin-33; C121766:MRE11 protein, human; D000076228:MRE11 Homologue Protein