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M-CSF induces monocyte survival by activating NF-κB p65 phosphorylation at Ser276 via protein kinase C

Yijie Wang1, Xiaokui Mo, Melissa G Piper

  • 1Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.

Plos One
|January 5, 2012
PubMed

Insights

Macrophage colony-stimulating factor (M-CSF) activates Nuclear Factor-kappaB (NF-κB) via conventional protein kinase C (PKC) pathways. This identifies PKC as crucial for M-CSF-driven macrophage survival and NF-κB signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophage colony-stimulating factor (M-CSF) is vital for mononuclear phagocyte survival and proliferation.
  • Nuclear Factor-kappaB (NF-κB) transcription factor regulates genes critical for M-CSF-induced macrophage survival.

Purpose of the Study:

  • To elucidate the mechanism of NF-κB transcriptional activation by M-CSF.
  • To identify the specific kinases involved in M-CSF-mediated NF-κB signaling.

Main Methods:

  • Utilized human monocyte-derived macrophages (MDMs) and RAW 264.7 cells.
  • Employed protein kinase C (PKC) inhibitors (Ro-31-8220, Gö-6976), dominant-negative PKCα constructs, and PKCα siRNA.
  • Assessed NF-κB transcriptional activity and NF-κB p65 phosphorylation at Ser276.

Main Results:

  • M-CSF stimulated NF-κB transcriptional activity in both cell types.
  • PKC inhibition and knockdown reduced M-CSF-induced NF-κB activity and monocyte survival.
  • PKCα was identified as a key upstream kinase, mediating NF-κB p65 Ser276 phosphorylation.

Conclusions:

  • Conventional PKCs, particularly PKCα, are essential upstream regulators of M-CSF-induced NF-κB activation.
  • PKCα-mediated phosphorylation of NF-κB p65 at Ser276 is critical for macrophage survival and NF-κB signaling.
  • NF-κB p65 Ser276 phosphorylation is important for both basal and M-CSF-stimulated NF-κB activation in human macrophages.

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