Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2

Rong L. He, Jian Zhou, Crystal Z. Hanson, Jia Chen, Ni Cheng, Richard D. Ye

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

The acute-phase protein serum amyloid A (SAA) is commonly considered a marker for inflammatory diseases; however, its precise role in inflammation and infection, which often result in neutrophilia, remains ambiguous. In this study, we demonstrate that SAAis a potent endogenous stimulator of granulocyte colony-stimulated factor (G-CSF), a principal cytokine-regulating granulocytosis. This effect of SAA is dependent on Toll-like receptor 2 (TLR2). Our data demonstrate that, in mouse macrophages, both G-CSF mRNA and protein were significantly increased after SAA stimulation. The induction of G-CSF was blocked by an anti-TLR2 antibody and markedly decreased in the TLR2-deficient macrophages. SAA stimulation results in the activation of nuclear factor-κB and binding activity to the CK-1 element of the G-CSF promoter region. In vitro reconstitution experiments also support that TLR2 mediates SAA-induced G-CSF expression. In addition, SAA-induced secretion of G-CSF was sensitive to heat and proteinase K treatment, yet insensitive to polymyxin B treatment, indicating that the induction is a direct effect of SAA. Finally, our in vivo studies confirmed that SAA treatment results in a significant increase in plasma G-CSF and neutrophilia, whereas these responses are ablated in G-CSF- or TLR2-deficient mice.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalBlood
Volume113
Issue number2
DOIs
StatePublished - Jan 8 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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