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Beta Interferon Production Is Regulated by p38 Mitogen-Activated Protein Kinase in Macrophages via both MSK1/2- and

Victoria A McGuire1,2, Dalya Rosner3, Olga Ananieva1

  • 1MRC Protein Phosphorylation Unit, School of Life Sciences, Sir James Black Centre, University of Dundee, Dundee, United Kingdom.

Molecular and Cellular Biology
|November 1, 2016
PubMed

Insights

Mitogen- and stress-activated kinases 1 and 2 (MSK1/2) negatively regulate beta interferon (IFN-β) in macrophages. This regulation occurs via dual-specificity phosphatase 1 (DUSP1), impacting inflammatory responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Beta interferon (IFN-β) signaling in macrophages is crucial for pathogen response but tightly regulated to prevent pathological outcomes.
  • Autocrine and paracrine IFN-β signaling forms a feedback loop essential for macrophage activation by pathogen-associated molecular patterns.

Purpose of the Study:

  • To investigate the role of mitogen- and stress-activated kinases 1 and 2 (MSK1/2) in the negative regulation of macrophage IFN-β expression.
  • To elucidate the molecular mechanisms by which MSK1/2 control IFN-β production.

Main Methods:

  • Utilized MSK1/2 knockout mice and macrophages to assess IFN-β expression.
  • Investigated the involvement of dual-specificity phosphatase 1 (DUSP1), p38, and Jun N-terminal kinase (JNK) pathways.
  • Analyzed the phosphorylation of transcription factors and the stability of IFN-β mRNA.

Main Results:

  • Macrophage expression of IFN-β was significantly elevated in MSK1/2 knockout models.
  • MSK1/2 inhibit IFN-β expression through the induction of DUSP1, which inactivates p38 and JNK.
  • Overexpression of IFN-β in MSK1/2 and DUSP1 knockout macrophages involved JNK-mediated c-jun activation and p38-mediated inactivation of tristetraprolin.

Conclusions:

  • MSK1/2 act as negative regulators of macrophage IFN-β production.
  • The MSK1/2-DUSP1 axis is a key pathway controlling IFN-β expression and inflammatory responses.
  • Understanding this regulatory mechanism provides insights into managing excessive inflammation.
Keywords:
CREBDUSP1MSK1MSK2TTPbeta interferonp38 kinases

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