IADR Abstract Archives

Interleukin-18 Receptor Regulation by TNF- alpha

Periodontitis and rheumatoid arthritis are both chronic inflammatory diseases sharing similar cytokine profiles. Interleukin 18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-alpha) play a pivotal role in disease progression. This is evident by gene targeting and cytokine blocking in both animal model systems and clinical therapy of inflammatory diseases. It has been shown that a human monocytic cell line (KG-1) responds to IL-18 for the production IFN-gamma, which is facilitated by TNF-alpha priming. This effect is due to the up-regulation of cell surface IL-18R alpha and beta chains. Objective: The aim of this study is to clarify the molecular mechanism of TNF-alpha and other factors involved in the regulation of IL-18 responses of human monocytes via the regulation of IL-18 receptors. Methods: TNF-alpha pre-stimulated KG-1 cells were cultured with increasing concentrations of recombinant human IL-18. IFN-gamma production was determined by ELISA. The copy numbers of the mRNA for both IL-18R alpha and beta chains were measured by RT-PCR and qPCR. Both cell surface and intracellular amount of IL-18R alpha and beta chains were examined by FACS. Results: 1) Higher concentration of IL-18 alone can stimulate IFN-gamma production from KG-1 cells. However, TNF-alpha pre-stimulation sensitized KG-1 to produce 5 times more IFN-gamma. 2) IL-18R alpha mRNA was up-regulated about 10 times by TNF-alpha priming, while IL-18R beta was not. 3) Both IL-18R alpha and beta protein surface expression was induced by TNF-alpha stimulation. Conclusion: This study indicates that TNF-alpha is another important factor that regulates IL-18 responses in inflammatory diseases, via regulation of IL-18R expression. TNF-alpha induces both the mRNA and protein expression of IL-18R alpha, but only the protein level of IL-18R beta chain. This indicates that IL-18R beta cell surface translocation may be controlled by IL-18R alpha expression.
Pan European Federation Meeting
2006 Pan European Federation Meeting (Dublin, Ireland)
Dublin, Ireland
2006
164
Scientific Groups
  • Koutoulaki, Anna  ( Cardiff University, Cardiff, N/A, United Kingdom )
  • Aeschlimann, Daniel P.  ( Cardiff University, Cardiff, N/A, United Kingdom )
  • Wei, Xiao-qing  ( Cardiff University, Cardiff, N/A, United Kingdom )
  • Poster Session
    I. Microbiology Posters I
    09/13/2006