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Membrane interleukin-18 revisits membrane IL-1α in T-helper type 1 responses

Charles A Dinarello1

  • 1University of Colorado Denver, Division of Infectious Diseases, B168, 12700 East 19th Ave., Auroia, CO 80045, USA. cdinarello@mac.com

European Journal of Immunology
|June 9, 2012
PubMed

Insights

Interleukin-18 (IL-18) functions as a membrane protein on macrophages, inducing IFN-γ from NK cells upon LPS stimulation. This finding highlights IL-18

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Cytokine-receptor interactions are typically studied using soluble forms.
  • Membrane-bound cytokines can mediate biological activity through cell-cell contact.
  • Interleukin-18 (IL-18) is a key cytokine for inducing T-helper 1 (Th1) responses.

Purpose of the Study:

  • To investigate the membrane-bound form of Interleukin-18 (IL-18).
  • To determine the biological activity of membrane-bound IL-18 in human macrophages.
  • To elucidate the mechanism of IL-18-mediated immune cell activation.

Main Methods:

  • Utilized M-CSF-differentiated human macrophages.
  • Investigated IL-18 expression and localization on the cell membrane.
  • Assessed the induction of Interferon-gamma (IFN-γ) from Natural Killer (NK) cells upon lipopolysaccharide (LPS) stimulation.
  • Examined the role of caspase-1 in the observed IL-18 activity.

Main Results:

  • Interleukin-18 (IL-18) was identified as an integral membrane protein on M-CSF-differentiated human macrophages.
  • LPS stimulation led to IL-18-mediated induction of Interferon-gamma (IFN-γ) from NK cells.
  • This induction was dependent on caspase-1 activity.

Conclusions:

  • Membrane-bound IL-18 plays a significant role in immune cell communication.
  • The findings have substantial immunological and inflammatory implications, particularly for Th1-mediated immunity.
  • Caspase-1 is crucial for the function of membrane-bound IL-18 in inducing IFN-γ.

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