Induction of Samhd1 by interferon gamma and lipopolysaccharide in murine macrophages requires IRF1. 2020

Lorena Valverde-Estrella, and Martí López-Serrat, and Guillem Sánchez-Sànchez, and Tania Vico, and Jorge Lloberas, and Antonio Celada
Macrophage Biology Group, Department of Cellular Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.

SAMHD1 is an enzyme with phosphohydrolase activity. Mutations in SAMHD1 have been linked to the development of Aicardi-Goutières syndrome in humans. This enzyme also has the capacity to restrict HIV virus replication in macrophages. Here, we report that Samhd1 is highly expressed in murine macrophages and is regulated by proinflammatory (IFN-γ and LPS) but not by anti-inflammatory (IL-4 or IL-10) activators. The induction of Samhd1 follows the pattern of an intermediate gene that requires protein synthesis. In transient transfection experiments using the Samhd1 promoter, we found that a fragment of 27 bps of this gene, falling between -937 and -910 bps relative to the transcription start site, is required for IFN-γ-dependent activation. Using EMSAs, we determined that IFN-γ treatment led to the elimination of a protein complex. Chromatin immunoprecipitation assays and siRNA experiments revealed that IRF1 is required for IFN-γ- or LPS-induced Samhd1 expression. Therefore, our results indicate that Samhd1 is stimulated by proinflammatory agents IFN-γ and LPS. Moreover, they reveal that these two agents, via IRF1, eliminate a protein complex that may be related to a repressor, thereby, triggering Samhd1 expression.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000076106 SAM Domain and HD Domain-Containing Protein 1 A host restriction triphosphorylhydrolase and dNTPase that contains an N-terminal STERILE ALPHA MOTIF and central, conserved ASPARTATE and HISTIDINE (HD) domain. It acts on single-stranded RNA, yielding deoxynucleosides and triphosphate, and functions in anti-viral defense through its dNTPase activity, reducing cellular dNTP levels below what is required for retroviral reverse transcription in DENDRITIC CELLS and MYELOID CELLS. It also has RIBONUCLEASE activity which blocks early replication of retroviruses such as HIV-1. Mutations in the SAMHD1 gene are associated with type 5 Aicardi-Goutieres syndrome (AGS5) and type 2 chilblain LUPUS (CHBL2). SAMHD1 Deoxynucleoside Triphosphate Triphosphohydrolase,SAMHD1 Protein,SAMHD1 dNTPase,SAM Domain and HD Domain Containing Protein 1
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D050856 Interferon Regulatory Factor-1 An interferon regulatory factor that binds upstream TRANSCRIPTIONAL REGULATORY ELEMENTS in the GENES for INTERFERON-ALPHA and INTERFERON-BETA. It functions as a transcriptional activator for the INTERFERON TYPE I genes. IRF-1 Transcription Factor,IREBF1 Protein,IREBF1 Transcription Factor,IRF-1 Protein,ISGF1 Transcription Factor,Interferon-Stimulated Gene Factor 1,MyD32 Protein,Factor, IRF-1 Transcription,Factor, ISGF1 Transcription,IRF 1 Protein,IRF 1 Transcription Factor,Interferon Regulatory Factor 1,Interferon Stimulated Gene Factor 1,Transcription Factor, IREBF1,Transcription Factor, IRF-1,Transcription Factor, ISGF1
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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