Actinobacillus actinomycetemcomitans-induced expression of IL-1 alpha and IL-1 beta in human gingival epithelial cells: role in IL-8 expression

Gingival epithelial cells (GEC) are the first cells of the host that encoun ter the periodontal pathogens, and therefore their role in the initiation o f the inflammatory response is critical. We aimed to: 1) characterize the e xpression of interleukin (IL)-1 alpha and IL-1 beta in human gingiva and cu ltured GEC; 2)demonstrate the ability of A. actinomycetemcomitans extracts to upregulate IL-1 alpha, IL-1 beta and IL-8 expression in GEC in vitro; an d 3) characterize the role of IL-1 alpha and IL-1 beta in the induction of IL-8 expression in GEC in vitro. Ten gingival biopsies (5 inflamed and 5 co ntrols) and cultured GEC were examined for IL-1 alpha and IL-1 beta using i mmunohistochemical techniques. GEC were also challenged with A. actinomycet emcomitans extracts or IL-1. and secretion of IL-1 and IL-8 was determined by ELISA. In vivo, IL-1 alpha and IL-1 beta were localized in the gingival epithelium and the infiltrating leukocytes. In vitro, A. actinomycetemcomit ans extracts induced a time-dependent expression of IL-1 alpha, IL-1 beta a nd IL-8 in GEC. IL-1 inhibitors did not affect A. actinomycetemcomitans-ind uced IL-8, although they inhibited IL-8 induced by IL-1 alpha or IL-1 beta. In conclusion, GEC are a major source of IL-1 alpha and IL-1 beta in the p eriodontium, which in turn induce additional inflammatory mediators such as IL-8. Therefore GEC can be a potential target for therapeutic intervention in the future.