Early growth response gene (EGR)-1 regulates leukotriene D4-induced cytokine transcription in Hodgkin lymphoma cells

Prostaglandins Other Lipid Mediat. 2015 Sep;121(Pt A):122-30. doi: 10.1016/j.prostaglandins.2015.06.004. Epub 2015 Jun 23.

Abstract

Classical Hodgkin lymphoma (cHL) has a unique pathological feature characterized by a minority of malignant Hodgkin Reed-Sternberg (H-RS) cells surrounded by numerous inflammatory cells. Cysteinyl-leukotrienes (CysLTs) are produced by eosinophils, macrophages and mast cells in the HL tumor microenvironment. In the present study we have explored the signal transduction pathways leading to leukotriene (LT) D4 induced expression of cytokines in the Hodgkin lymphoma cell line L1236 and KM-H2. Stimulation of L1236 and KM-H2 cells with LTD4 led to a concentration- and time-dependent increase at the transcriptional level of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3) and CCL4. The expression of several transcription factors was induced upon stimulation of Hodgkin cell lines with LTD4. Among these, EGR-1 was required for cytokine production. Inhibition of EGR-1 expression using shEGR-1 transduced by lentivirus led to suppression of the expression of TNF-α and IL-6. The effect of LTD4 on the expression of transcription factors and cytokines were also blocked by the specific CysLT1 receptor antagonist zafirlukast. These results demonstrate that EGR-1 plays a critical role in LTD4-induced cytokine transcription in Hodgkin cell lines.

Keywords: Cysteinyl leukotriene receptors; Early growth response 1; Hodgkin lymphoma; Leukotrienes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytokines / genetics*
  • Early Growth Response Protein 1 / deficiency
  • Early Growth Response Protein 1 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hodgkin Disease / genetics
  • Hodgkin Disease / pathology*
  • Humans
  • Leukotriene D4 / pharmacology*
  • Receptors, Leukotriene / metabolism
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects*

Substances

  • Cytokines
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Receptors, Leukotriene
  • Leukotriene D4
  • leukotriene D4 receptor