Chemotactic effect of S100A8 and S100A9 on human eosinophilic leukemia cells, EoL-1 through TLR4

Abstract

S100A8 and S100A9 function as key factors in inflammatory responses including cell survival, differentiation and chemotactic activity. Chronic eosinophilic leukemia (CEL) is a rare hematological malignancy with eosinophilia. In this study, we investigated the contribution of S100A8 and S100A9 to chemotaxis of the human eosinophilic leukemia cell line, EoL-1. A chemotaxis assay, western blot analysis and a NF-κB transcription factor assay were conducted to investigate the chemotactic mechanism. S100A8 and S100A9 induced the migration of EoL-1 cells via the phosphorylation of PKCδ, AKT, and MAPKs and the translocation of NF-κB; however, they had no effect on eosinophils from normal peripheral blood. PKCδ, AKT, and MAPKs such as ERK, p38 MAPK, and JNK are upstream regulator molecules of NF-κB activation. Iκ-Bα degradation is needed for NF-κB activation. These findings suggest that S100A8 and S100A9 induce the cell movement and contribute to an understanding of S100A8 and S100A9 in eosinophil biology and the pathogenic mechanism of hematological malignancy.