LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils.
10.3858/emm.2009.41.5.036
- Author:
Ha Young LEE
1
;
Sang Doo KIM
;
Jae Woong SHIM
;
Sun Young LEE
;
Jeanho YUN
;
Yoe Sik BAE
Author Information
1. Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Korea. yoesik@donga.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
CAP18 lipopolysaccharide-binding protein;
FPR2 protein, human;
interleukin-8;
mitogen-activated protein kinases;
neutrophils;
serum amyloid A protein
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(5):325-333
- CountryRepublic of Korea
- Language:English
-
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.
