Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo /631/45/612 /631/250 /38 /82 /82/80 article

Byung Cheon Lee, Sang Goo Lee, Min Kyung Choo, Ji Hyung Kim, Hae Min Lee, Sorah Kim, Dmitri E. Fomenko, Hwa Young Kim, Jin Mo Park, Vadim N. Gladyshev

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number5119
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Selenoproteins
Methionine Sulfoxide Reductases
Methionine
Anti-Inflammatory Agents
Macrophages
Cytokines
Gene Expression
Lipopolysaccharides
Proteins
Interleukin-1 Receptors
Post Translational Protein Processing
Selenium
Cellular Immunity
Interleukin-10
Oxidation-Reduction
Immunity
Inflammation
Enzymes

ASJC Scopus subject areas

  • General

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Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo /631/45/612 /631/250 /38 /82 /82/80 article. / Lee, Byung Cheon; Lee, Sang Goo; Choo, Min Kyung; Kim, Ji Hyung; Lee, Hae Min; Kim, Sorah; Fomenko, Dmitri E.; Kim, Hwa Young; Park, Jin Mo; Gladyshev, Vadim N.

In: Scientific reports, Vol. 7, No. 1, 5119, 01.12.2017.

Research output: Contribution to journalArticle

Lee, Byung Cheon ; Lee, Sang Goo ; Choo, Min Kyung ; Kim, Ji Hyung ; Lee, Hae Min ; Kim, Sorah ; Fomenko, Dmitri E. ; Kim, Hwa Young ; Park, Jin Mo ; Gladyshev, Vadim N. / Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo /631/45/612 /631/250 /38 /82 /82/80 article. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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