The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.
Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.
Lee
Ji-Sook
JS
Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 301-746, Republic of Korea.
Yang
Eun Ju
EJ
Kim
In Sik
IS
D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism*; D004789:Enzyme Activation; D004804:Eosinophils / Q000201:enzymology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D018932:Chemokine CCL2; D016328:NF-kappa B; D051745:Protein Kinase C-delta