The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells
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Published on: June 6, 2025
Ji-Sook Lee1, Eun Ju Yang, In Sik Kim
1Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 301-746, Republic of Korea.
Abstract:
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.
Insights
Monocyte chemoattractant protein-1 (MCP-1) drives eosinophilic leukemia cell movement and survival. Protein kinase C delta (PKC delta) plays a key role in these MCP-1-mediated effects, impacting eosinophil disorders.
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- Idiopathic hypereosinophilic syndrome (HES) involves clonal eosinophil proliferation.
- The FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) fusion gene is crucial in HES pathogenesis.
- Monocyte chemoattractant protein-1 (MCP-1)/CCL2 and protein kinase C delta (PKC delta) roles in eosinophil biology require further investigation.
Purpose of the Study:
- To investigate the contribution of MCP-1/CCL2 to chemotactic activity.
- To explore the role of PKC delta in the human eosinophilic leukemia cell line EoL-1.
- To elucidate the signaling pathways involved in MCP-1-induced EoL-1 cell migration and survival.
Main Methods:
- Utilized the human eosinophilic leukemia cell line EoL-1, which expresses CCR2.
- Stimulated EoL-1 cells with MCP-1 to analyze chemotaxis and intracellular signaling.
- Investigated the involvement of G(i)/G(o) proteins, phospholipase C (PLC), PKC delta, p38 MAPK, and NF-kappaB.
Main Results:
- MCP-1 induced significant migration of EoL-1 cells.
- The MCP-1 signaling pathway involves G(i)/G(o) protein, PLC, PKC delta, p38 MAPK, and NF-kappaB.
- PKC delta activation inhibited NF-kappaB translocation and suppressed apoptosis in EoL-1 cells by inhibiting caspase 3 and caspase 9.
Conclusions:
- MCP-1 is a key chemoattractant for eosinophilic leukemia cells.
- PKC delta acts as an anti-apoptotic molecule in EoL-1 cells and mediates MCP-1-induced cell movement.
- This study enhances understanding of MCP-1 in eosinophil biology and the pathogenesis of eosinophilic disorders.
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