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Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling

Kavita Bisht1, Barbara Wegiel2, Jens Tampe3

  • 1Heart Foundation Research Center, Griffith Health Institute, Griffith University, Gold Coast, Australia; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

Biochemical and Biophysical Research Communications
|May 13, 2014
PubMed

Insights

Biliverdin, a heme breakdown product, reduces inflammatory responses by inhibiting complement receptor 5a (C5aR) expression in macrophages. This anti-inflammatory effect is mediated through the mammalian target of rapamycin (mTOR) pathway.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Macrophages are key regulators of inflammation, expressing diverse pro- and anti-inflammatory molecules.
  • Complement receptor 5a (C5aR) is implicated in inflammatory disorder development.
  • Biliverdin and bilirubin, heme catabolism products, possess anti-inflammatory properties and inhibit complement activation.

Purpose of the Study:

  • To investigate the effects of biliverdin on complement receptor 5a (C5aR) expression in macrophages.
  • To elucidate the roles of Akt and mammalian target of rapamycin (mTOR) signaling in biliverdin's effects on C5aR expression.

Main Methods:

  • Administration of biliverdin to macrophages.
  • Lipopolysaccharide (LPS) stimulation to induce inflammatory responses.
  • Assessment of C5aR expression.
  • Inhibition of mTOR signaling using rapamycin.

Main Results:

  • Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression in macrophages.
  • This inhibition was partially reversed by rapamycin, indicating involvement of the mTOR pathway.
  • Biliverdin also reduced LPS-dependent expression of pro-inflammatory cytokines TNF-α and IL-6.

Conclusions:

  • Biliverdin regulates LPS-mediated C5aR expression through the mTOR signaling pathway.
  • This finding reveals a novel mechanism for biliverdin's anti-inflammatory actions.
  • Biliverdin represents a potential therapeutic agent for inflammatory conditions.
Keywords:
InflammationMacrophagemTOR

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