Interleukin-8 and Intercellular Adhesion Molecule 1 Regulation in Oral Epithelial Cells by Selected Periodontal Bacteria: Multiple Effects ofPorphyromonas gingivalisvia Antagonistic Mechanisms

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Abstract
Interaction of bacteria with mucosal surfaces can modulate the production of proinflammatory cytokines and adhesion molecules produced by epithelial cells. Previously, we showed that expression of interleukin-8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) by gingival epithelial cells increases following interaction with several putative periodontal pathogens. In contrast, expression of IL-8 and ICAM-1 is reduced afterPorphyromonas gingivalisATCC 33277 challenge. In the present study, we investigated the mechanisms that govern the regulation of these two molecules in bacterially infected gingival epithelial cells. Experimental approaches included bacterial stimulation of gingival epithelial cells by either a brief challenge (1.5 to 2 h) or a continuous coculture throughout the incubation period. The kinetics of IL-8 and ICAM-1 expression following brief challenge were such that (i) secretion of IL-8 by gingival epithelial cells reached its peak 2 h followingFusobacterium nucleatuminfection whereas it rapidly decreased within 2 h afterP. gingivalisinfection and remained decreased up to 30 h and (ii) IL-8 and ICAM-1 mRNA levels were up-regulated rapidly 2 to 4 h postinfection and then decreased to basal levels 8 to 20 h after infection with eitherActinobacillus actinomycetemcomitans,F. nucleatum, orP. gingivalis. Attenuation of IL-8 secretion was facilitated by adherentP. gingivalisstrains. The IL-8 secreted from epithelial cells afterF. nucleatumstimulation could be down-regulated by subsequent infection withP. gingivalisor its culture supernatant. Although these results suggested that IL-8 attenuation at the protein level might be associated withP. gingivalisproteases, the Arg- and Lys-gingipain proteases did not appear to be solely responsible for IL-8 attenuation. In addition, whileP. gingivalisup-regulated IL-8 mRNA expression, this effect was overridden when the bacteria were continuously cocultured with the epithelial cells. The IL-8 mRNA levels in epithelial cells following sequential challenge withP. gingivalisandF. nucleatumand vice versa were approximately identical and were lower than those followingF. nucleatumchallenge alone and higher than control levels or those followingP. gingivalischallenge alone. Thus, together with the protease effect,P. gingivalispossesses a powerful strategy to ensure the down-regulation of IL-8 and ICAM-1.

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