Hepcidin regulation by BMP signaling in macrophages is lipopolysaccharide dependent

Xinggang Wu1, Lai-Ming Yung, Wai-Hang Cheng

  • 1School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Plos One
|October 3, 2012
PubMed

Insights

Bone morphogenetic proteins (BMPs) do not directly regulate hepcidin in macrophages. Instead, BMPs enhance lipopolysaccharide (LPS)-induced hepcidin expression via NF-κB signaling, indicating distinct macrophage regulation.

Area of Science:

  • * Iron metabolism and antimicrobial peptide regulation.
  • * Cellular signaling pathways in innate immunity.

Background:

  • * Hepcidin, an antimicrobial peptide, regulates systemic iron levels by controlling iron absorption and macrophage iron release.
  • * Hepcidin synthesis primarily occurs in the liver, influenced by iron, inflammation, and hypoxia.
  • * Bone morphogenetic protein (BMP)-hemojuvelin (HJV)-SMAD signaling is established as a key regulator of hepcidin in hepatocytes.

Purpose of the Study:

  • * To investigate the role of BMP signaling in regulating hepcidin expression in macrophages.
  • * To determine if BMPs influence hepcidin expression in macrophages, similar to their role in hepatocytes.

Main Methods:

  • * Examined hepcidin expression in RAW 264.7, J774 macrophage cell lines, and primary peritoneal macrophages.
  • * Assessed the effects of BMP4 and BMP6, alone and in combination with lipopolysaccharide (LPS).
  • * Utilized Smad1/5/8 phosphorylation, Id1 expression, and NF-κB inhibition (Ro1069920) to analyze signaling pathways.

Main Results:

  • * BMP4 or BMP6 alone did not affect hepcidin expression in macrophages, despite activating Smad1/5/8 phosphorylation and Id1 expression.
  • * In the presence of LPS, BMP4 and BMP6 significantly stimulated hepcidin expression in macrophages.
  • * This BMP- and LPS-induced hepcidin stimulation was abolished by the NF-κB inhibitor Ro1069920.

Conclusions:

  • * Hepcidin regulation in macrophages differs from that in hepatocytes.
  • * BMPs regulate hepcidin expression in macrophages in a manner dependent on both LPS and NF-κB signaling.
  • * Findings reveal a novel LPS-NF-κB-dependent pathway for BMP-mediated hepcidin regulation in macrophages.

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