| First Author | He RL | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 2 | Pages | 429-37 |
| PubMed ID | 18952897 | Mgi Jnum | J:144859 |
| Mgi Id | MGI:3832110 | Doi | 10.1182/blood-2008-03-139923 |
| Citation | He RL, et al. (2009) Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2. Blood 113(2):429-37 |
| abstractText | 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. |
