Soluble CD14 induces cytokine release by human oral epithelial cells

Background and Objective: The epithelial cell barrier is the first line of host defense against bacterial aggression in periodontal sites. In view of the fact that oral epithelial cells do not express membrane CD14 and that high levels of the soluble form of the CD14 receptor have been detected in the gingival crevicular fluid of patients with periodontitis, we investigated the effects of recombinant soluble CD14 (rsCD14), alone and in combination with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) on the inflammatory response of human oral epithelial cells. Material and Methods: The oral epithelial cell line GMSM-K was stimulated with rsCD14, alone or in combination with A. actinomycetemcomitans LPS, and the levels of the inflammatory mediators interleukin (IL)-6, IL-8 and chemokine (C-C motif) ligand 5 (CCL5) were determined using ELISAs. Activation of the transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 was also monitored using ELISAs. Results: rsCD14 significantly induced the secretion of IL-6, IL-8 and CCL5 by oral epithelial cells. The combination of rsCD14 and A. actinomycetemcomitans LPS augmented this effect. Activation of the NF-kappa B pathway was significantly increased in epithelial cells treated with rsCD14 compared with a nonstimulated control, whereas there was no effect on the activation of activator protein-1. Conclusion: rsCD14 stimulated the inflammation cascade in oral epithelial cells, both alone or when associated with bacterial LPS, through an NF-kappa B-dependent pathway. This suggests that the presence of soluble CD14 in periodontitis lesions may contribute to the inflammatory process of periodontal disease.