Mechanisms of Actinobacillus actinomycetemcomitans-induced expression of interleukin-8 in gingival epithelial cells

Background: Gingival epithelial cells (GEC) are the first cells of the peri odontium to encounter known periodontal pathogens, such as Actinobacillus a ctinomycetemcomitans (A.a.) and, therefore, the role of this pathogen in th e initiation of the inflammatory response is critical. However, little is k nown about the interactions of A.a. with GEC. In the present study, the mec hanisms by which extracts from A.a. induced expression of the chemotactic c ytokine interleukin-8 (IL-8) in GEC, in vitro, were examined. Methods: An established GEC line, PP, was co-cultured with sonicated extrac ts of A.a. under various in vitro experimental conditions, and the IL-8 sec retion 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 sec retion (7-fold, P <0.01) was at the level of 50 mug/ml of A.a. extract. Tim e-course studies revealed a dramatic increase of IL-8 expression after 12 h ours of continuous stimulation. Pretreatment with polymyxin B (lipopolysacc haride [LPS] inhibitor) did not reduce the IL-8 expression induced by A.a. extracts (P >0.10). The introduction of p38 mitogen-activated protein kinas e (MAPK) inhibitor SB 203580 markedly inhibited (> 75%, P <0.01) A.a.-induc ed expression of IL-8. It is concluded that A.a. extracts upregulated the b asal IL-8 expression in GEC. Conclusions: The effect was LPS-independent and involved a p38 MAPK signal transducing pathway. Understanding mechanisms of proinflammatory cytokine i nduction is, important in periodontal pathology as it may lead to novel the rapeutic approaches for periodontitis, thus controlling host inflammatory r esponses.