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Scientists

Cooperative Activation of CCL5 Expression in Airway Epithelial Cells

Strategic Insights

— 1 min read

Scientists in Tokyo, Japan have made a significant discovery in the field of tumor necrosis factors. Their study, published in International Archives of Allergy and Immunology, reveals a complex mechanism by which CCL5 (RANTES) contributes to prolonged eosinophilic inflammation and asthma exacerbation after a viral infection. The researchers found that Toll-like receptor 3 (TLR3) and inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), play a crucial role in regulating CCL5 expression in airway epithelial cells.

Key Takeaways:

  • CCL5/RANTES is a key contributor to prolonged eosinophilic inflammation and asthma exacerbation after a viral infection.
  • The airway epithelial cell line BEAS-2B was used in the study to determine the levels of CCL5 mRNA and CCL5 protein expression.
  • Synthetic double-stranded RNA (dsRNA) up-regulated the expression of CCL5 mRNA and CCL5 protein, and adding TNF-alpha or IFN-gamma further increased CCL5 expression.
  • The combination of TNF-alpha and dsRNA cooperatively activated the CCL5 promoter region and the NF-kappaB-specific reporter.
  • IFN-gamma increased the stability of CCL5 mRNA induced by dsRNA, but did not activate NF-kappaB.
  • Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CCL5 in airway epithelial cells.
  • TNF-alpha may activate NF-kappaB in cooperation with TLR3 signaling, while IFN-gamma may stabilize CCL5 mRNA up-regulated by TLR3.

Statistics:

  • CCL5 mRNA and protein expression were determined using real-time PCR and ELISA.
  • DNase treatment of the reporter plasmids reduced transcriptional activity to that of the promoter-less vector (pGL3-Basic).
  • Luciferase activity was measured in the cells transfected with the reporter plasmids.
  • Phosphorylation of STAT-1 was analyzed by Western blot, and the effects of IFN-gamma were not evident in the cells transfected with short interfering RNA for STAT-1.

Sources:

  • Cooperative activation of CCL5 expression by TLR3 and tumor necrosis factor-alpha or interferon-gamma through nuclear factor-kappaB or STAT-1 in airway epithelial cells. International Archives of Allergy and Immunology, 2010;152 Suppl():9-17).
  • Tumor Necrosis Factors.

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