Premium
Induction of Samhd1 by interferon gamma and lipopolysaccharide in murine macrophages requires IRF1
Author(s) -
ValverdeEstrella Lorena,
LópezSerrat Martí,
SánchezSànchez Guillem,
Vico Tania,
Lloberas Jorge,
Celada Antonio
Publication year - 2020
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201948491
Subject(s) - samhd1 , irf1 , biology , proinflammatory cytokine , chromatin immunoprecipitation , microbiology and biotechnology , transcription (linguistics) , transfection , repressor , immunoprecipitation , interferon gamma , lipopolysaccharide , transcription factor , gene expression , reverse transcriptase , gene , inflammation , promoter , cytokine , genetics , immunology , rna , linguistics , philosophy
Abstract 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.