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KMID : 0620920090410050325
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Experimental & Molecular Medicine
2009 Volume.41 No. 5 p.325 ~ p.333
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LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils
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Lee Ha-Young
Yun Jean-Ho
Bae Yoe-Sik
Kim Sang-Doo
Shim Jae-Woong
Lee Sun-Young
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Abstract
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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.
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KEYWORD
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CAP18 lipopolysaccharide-binding protein, FPR2 protein, human, interleukin-8, mitogen-activatedprotein kinases, neutrophils, serum amyloid A protein
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