title: Microarray analysis reveals that Type I interferon strongly increases the expression of immune-response related genes in Ubp43 (Usp18) deficient macrophages.
abstract: Type I interferon (IFN) contributes significantly to innate immune responses to pathogen infections in macrophages. Our previous studies demonstrate that Ubp43, an ISG15-specific isopeptidase, is highly expressed in macrophages and noncatalytically inhibits Type I IFN signaling. To understand the effect of Type I IFN and Ubp43 in macrophage activation, we analyzed the expression of IFN-beta stimulated genes in wild-type and Ubp43(-/-) bone marrow derived macrophages (BMMs). Here, we show that Ubp43 regulates IFN-beta stimulated genes at genome level. IFN hypersensitivity of Ubp43(-/-) BMMs resulted in the identification of 749 unique genes that are upregulated by IFN-beta, including a large group of previously unidentified IFN-stimulated genes. Functional analyses of these genes showed that Type I IFN strongly induced the expression of a group of immune response related genes, including genes for antigen presentation, antiviral responses, and chemokine and cytokine production. These results provide excellent biochemical support for the high resistance of viral and bacterial infection of Ubp43 knockout mice, suggesting that Ubp43 is a potential therapeutic target for the enhancement of immune responses against infections.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zou
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Adedayo
authors.initials: A
authors.lastname: Handidu
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Keun Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Dong-Er
authors.initials: DE
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016000:Cluster Analysis; D010450:Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D007109:Immunity / Q000235:genetics*; D007370:Interferon Type I / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D043222:Ubiquitin Thiolesterase; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D007370:Interferon Type I; D016899:Interferon-beta; D010450:Endopeptidases; C118306:Usp18 protein, mouse; D043222:Ubiquitin Thiolesterase