The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells

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.

Cytokine
|August 12, 2009
PubMed

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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