Exp Mol Med.  2009 May;41(5):325-333. 10.3858/emm.2009.41.5.036.

LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils

• Lee HY
• Kim SD
• Shim JW
• Lee SY
• Yun J
• Bae YS

• KMID: 1123806
• DOI: http://doi.org/10.3858/emm.2009.41.5.036

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.

Keyword

CAP18 lipopolysaccharide-binding protein; FPR2 protein, human; interleukin-8; mitogen-activated protein kinases; neutrophils; serum amyloid A protein

MeSH Terms

Animals
Antimicrobial Cationic Peptides/*pharmacology
Cell Line, Tumor
Cell Movement
Chemotaxis, Leukocyte
Humans
Interleukin-8/*biosynthesis
MAP Kinase Kinase Kinases/metabolism
Neutrophils/drug effects/*immunology
Proto-Oncogene Proteins/metabolism
Rats
Receptors, Formyl Peptide/metabolism
Receptors, Lipoxin/metabolism
Serum Amyloid A Protein/*antagonists & inhibitors
Signal Transduction
Transcription, Genetic