BACKGROUND Gingival epithelial cells (GEC) are the first cells of the periodontium to encounter known periodontal pathogens, such as Actinobacillus actinomycetemcomitans (A.a.) and, therefore, the role of this pathogen in the initiation of the inflammatory response is critical. However, little is known about the interactions of A.a. with GEC. In the present study, the mechanisms by which extracts from A.a. induced expression of the chemotactic cytokine interleukin-8 (IL-8) in GEC, in vitro, were examined. METHODS An established GEC line, PP, was co-cultured with sonicated extracts of A.a. under various in vitro experimental conditions, and the IL-8 secretion was determined with enzyme-linked immunosorbent assay. RESULTS A.a. extracts induced a time- and dose-dependent expression of IL-8 from the cells. Dose-response studies indicated that the highest IL-8 secretion (7-fold, P < 0.01) was at the level of 50 micrograms/ml of A.a. extract. Time-course studies revealed a dramatic increase of IL-8 expression after 12 hours of continuous stimulation. Pretreatment with polymyxin B (lipopolysaccharide [LPS] inhibitor) did not reduce the IL-8 expression induced by A.a. extracts (P > 0.10). The introduction of p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 markedly inhibited (> 75%, P < 0.01) A.a.-induced expression of IL-8. It is concluded that A.a. extracts upregulated the basal IL-8 expression in GEC. CONCLUSIONS The effect was LPS-independent and involved a p38 MAPK signal transducing pathway. Understanding mechanisms of proinflammatory cytokine induction is important in periodontal pathology as it may lead to novel therapeutic approaches for periodontitis, thus controlling host inflammatory responses.