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

نویسندگان

  • Rong L He
  • Jian Zhou
  • Crystal Z Hanson
  • Jia Chen
  • Ni Cheng
  • Richard D Ye
چکیده

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 SAA is 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-kappaB 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.

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

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عنوان ژورنال:
  • Blood

دوره 113 2  شماره 

صفحات  -

تاریخ انتشار 2009