Abstract
Serum amyloid A (SAA) has been regarded as an important mediator of inflammatory responses. The effect of several formyl peptide receptor-like 1 (FPRL1) ligands on the production of IL-8 by SAA was investigated in human neutrophils. Among the ligands tested, LL-37 was found to specifically inhibit SAA-induced IL-8 production in transcriptional and post-transcriptional levels. Since SAA stimulated IL-8 production via ERK and p38 MAPK in human neutrophils, we tested the effect of LL-37 on SAA induction for these two MAPKs. LL-37 caused a dramatic inhibition of ERK and p38 MAPK activity, which is induced by SAA. LL-37 was also found to inhibit SAA-stimulated neutrophil chemotactic migration. Further, the LL-37-induced inhibitory effect was mediated by FPRL1. Our findings indicate that LL-37 is expected to be useful in the inhibition of SAA signaling and for the development of drugs against SAA-related inflammatory diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 325-333 |
| Number of pages | 9 |
| Journal | Experimental and Molecular Medicine |
| Volume | 41 |
| Issue number | 5 |
| DOIs | |
| State | Published - 31 May 2009 |
| Externally published | Yes |
Keywords
- CAP18 lipopolysaccharide-binding protein
- FPR2 protein, human
- Interleukin-8
- Mitogen-activated protein kinases
- Neutrophils
- Serum amyloid A protein