LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils.
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.
Lee
Ha Young
HY
Department of Biochemistry, Dong-A University, Busan, Korea.
Kim
Sang Doo
SD
Shim
Jae Woong
JW
Lee
Sun Young
SY
Yun
Jeanho
J
Bae
Yoe-Sik
YS
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D054804:Cathelicidins; D045744:Cell Line, Tumor; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D014158:Transcription, Genetic
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C105101:FPR2 protein, human; D016209:Interleukin-8; D011518:Proto-Oncogene Proteins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D000685:Serum Amyloid A Protein; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human