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Interleukin-18 expression and modulation in human corneal epithelial cells.

G J Burbach1, S M Naik, J B Harten

  • 1Department of Dermatology, Emory University, Atlanta, GA 30322, USA.

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Human corneal epithelial cells produce Interleukin-18 (IL-18), a key factor in interferon-gamma (IFN-gamma) production. This discovery suggests IL-18

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Area of Science:

  • Ophthalmology
  • Immunology
  • Cell Biology

Background:

  • Interleukin-18 (IL-18) is a pro-inflammatory cytokine that induces interferon-gamma (IFN-gamma) production by T-cells.
  • The role of IL-18 in corneal inflammation is not well understood.
  • Expression of IL-18 in human corneal epithelial cells has not been previously reported.

Purpose of the Study:

  • To investigate whether human corneal epithelial cells can produce IL-18.
  • To determine if pro-inflammatory mediators modulate IL-18 expression in these cells.
  • To assess the potential role of corneal IL-18 in IFN-gamma-dependent inflammation.

Main Methods:

  • Northern blot analysis and ELISA were used to detect IL-18 mRNA and protein in human corneal epithelial cells (HCEC and HCET).
  • Cells were treated with lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), or poly (dI:dC) to assess modulation of IL-18 expression.
  • IL-18 bioactivity was measured using a leukocyte IFN-gamma induction assay, and IL-18 was localized in human cornea via immunohistochemistry.

Main Results:

  • Human corneal epithelial cells constitutively express IL-18 mRNA and bioactive protein.
  • Pro-inflammatory agents (LPS, PMA, poly (dI:dC)) upregulated IL-18 expression.
  • Immunohistochemistry confirmed IL-18 protein expression in the epithelial cells of whole human cornea.

Conclusions:

  • This study provides the first evidence that human corneal epithelial cells produce the IFN-gamma inducing factor IL-18.
  • Corneal IL-18 production is inducible by pro-inflammatory stimuli.
  • Corneal IL-18 may play a significant role in initiating IFN-gamma-mediated inflammatory responses within the cornea.