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Sci Rep. 2017 Jul 11;7(1):5119. doi: 10.1038/s41598-017-05230-2.

Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo.

Author information

1
College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea. cheonii@korea.ac.kr.
2
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
3
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
4
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA.
5
College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea.
6
Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE, 68588, USA.
7
Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu, 42415, South Korea.
8
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA. vgladyshev@rics.bwh.harvard.edu.

Abstract

Post-translational redox modification of methionine residues often triggers a change in protein function. Emerging evidence points to this reversible protein modification being an important regulatory mechanism under various physiological conditions. Reduction of oxidized methionine residues is catalyzed by methionine sulfoxide reductases (Msrs). Here, we show that one of these enzymes, a selenium-containing MsrB1, is highly expressed in immune-activated macrophages and contributes to shaping cellular and organismal immune responses. In particular, lipopolysaccharide (LPS) induces expression of MsrB1, but not other Msrs. Genetic ablation of MsrB1 did not preclude LPS-induced intracellular signaling in macrophages, but resulted in attenuated induction of anti-inflammatory cytokines, such as interleukin (IL)-10 and the IL-1 receptor antagonist. This anomaly was associated with excessive pro-inflammatory cytokine production as well as an increase in acute tissue inflammation in mice. Together, our findings suggest that MsrB1 controls immune responses by promoting anti-inflammatory cytokine expression in macrophages. MsrB1-dependent reduction of oxidized methionine in proteins may be a heretofore unrecognized regulatory event underlying immunity and inflammatory disease, and a novel target for clinical applications.

PMID:
28698597
PMCID:
PMC5506048
DOI:
10.1038/s41598-017-05230-2
[Indexed for MEDLINE]
Free PMC Article

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