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

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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.

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Ha, Y. L., Sang, D. K., Jae, W. S., Sun, Y. L., Yun, J., & Bae, Y. S. (2009). LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils. Experimental and Molecular Medicine, 41(5), 325–333. https://doi.org/10.3858/emm.2009.41.5.036

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