Interleukin-18 expression and modulation in human corneal epithelial cells

Purpose. The interferon-gamma -inducing factor Interleukin-18 (IL-18) is a recently described cytokine that appears to have multiple important pro-inf lammatory effects including the induction of interferon-gamma (IFN-gamma) b y activated T-cells. The expression of IL-18 by human cornea has not been p reviously reported. In the present study, we examine the possibility that h uman corneal epithelial cells are capable of producing this leukocyte-activ ating factor which may play an important role in IFN-gamma -dependent infla mmation responses in the cornea. Methods. Northern blot analysis and ELISA were used to investigate the in v itro expression of IL-18 mRNA and protein respectively in primary (HCEC) an d transformed human corneal epithelial cells (HCET). To determine if IL-18 expression was modulated by pro-inflammatory mediators., cells were treated with lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA) or sy nthetic double stranded RNA (poly dI:dC). IL-18 bioactivity was determined in a leukocyte interferon-gamma induction assay and IL-18 was immunolocaliz ed in whole human cornea by immunohistochemistry using a specific anti-IL-1 8 antibody. Results. IL-18 mRNA and bioactive protein was constitutively expressed by h uman corneal epithelial cells and upregulated by PMA, LPS and poly dI:dC. T he constitutive expression of IL-18 protein immunoreactivity was also demon strated in the epithelial cells of whole human cornea tissue. Conclusions. This is the first study demonstrating that corneal epithelial cells are capable of producing the IFN-gamma inducing factor IL-18. Increas ed bioactive corneal IL-18 production can be induced by a number of pro-inf lammatory agents and may play an important role in initiating gamma -interf eron-mediated inflammatory responses in the cornea.