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Augmentation of Actinobacillus actinomycetemcomitans Invasion of Human Oral Epithelial Cells and Up-Regulation of Interleukin-8 Production by Saliva CD14

Division of Oral Immunology,¹ Division of Periodontology and Endodontology,² Division of Oral Microbiology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai 980-8575,³ Department of Immunology and Medical Zoology, Kagoshima University Graduate School of Medicine, Kagoshima 890-8544, Japan⁴

Received 28 May 2003/ Returned for modification 8 July 2003/ Accepted 21 July 2003

It has recently been shown that human salivary glands constitutively express CD14, an important molecule in innate immunity, and that a soluble form of CD14 is secreted in saliva. The concentration of CD14 in parotid (a serous gland) saliva was comparable to that in normal serum and 10-fold the amount in whole saliva, although the physiological function of saliva CD14 remained unclear. Actinobacillus actinomycetemcomitans is a periodontopathic bacterium and is able to invade oral epithelial cells. The present study showed that upon exposure to live A. actinomycetemcomitans Y4 for 2 h, human oral epithelial HSC-2 cells produced interleukin-8 (IL-8) for a further 24 h and whole saliva augmented the production induced by A. actinomycetemcomitans Y4. Parotid saliva showed a more pronounced effect on the production of IL-8 than whole saliva. Neither saliva preparation itself had IL-8-inducing activity. Parotid saliva exhibited antibacterial activity against a low concentration of A. actinomycetemcomitans Y4, but recombinant CD14 did not show the activity. The internalization of A. actinomycetemcomitans Y4 into HSC-2 cells was inhibited by cytochalasin B, indicating that the process was actin dependent, and depletion of CD14 from parotid saliva inhibited the invasion and, as a consequence, inhibited production of IL-8. Furthermore, human recombinant CD14 augmented invasion and IL-8 production. These results suggest that saliva CD14 promoted the invasion of oral epithelial cells by A. actinomycetemcomitans and consequently augmented the production of IL-8, playing an important role in innate immunity in the oral cavity.

Editor: J. T. Barbieri

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