Gingival epithelial cells participate in periodontal inflammation and destruction, producing IL-6, which regulates osteoclastic bone resorption, and PGE2, which can stimulate IL-6 production, osteoclastogenesis, and attachment loss. Cranberry (Vaccinium macrocarpon) components inhibit pro-inflammatory activity of LPS-stimulated human macrophages and normal gingival fibroblasts, but little is known of its effects on human gingival epithelial cells. Objectives: determine cytotoxic effects of cranberry components ± periodontopathogen [Fusobacterium nucleatum (F.n.) and Porphyromonas gingivalis (P.g.)] LPS on human gingival epithelial cells, and their production of IL-6 and PGE2. Methods: Smulow-Glickman (S-G) human gingival epithelial cells were incubated with NDM (high molecular weight non-dialyzable material derived from cranberry juice; 1-500 µg/ml) or LPS (1 or 5 µg/ml) ± NDM in serum-free medium for ≤6d. Membrane damage was assessed by lactate dehydrogenase activity released into cell supernatants after short-term exposure; viability was assessed by activity of a mitochondrial enzyme after 1-6d exposure. IL-6 and PGE2 production after 6-day exposure were measured by ELISA. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. Results: Short-term (3-6 hr) exposure to NDM (1-500 µg/ml), or LPS ± NDM (1-500 µg/ml) caused no significant membrane damage. NDM (≤ 25 µg/ml) or LPS ± NDM (≤ 25 µg/ml) had no significant effect on viability at ≤ 6-d exposure. While neither F.n. nor P.g. LPS stimulated IL-6 or PGE2, NDM (≤ 25 µg/ml) or LPS ± NDM (≤ 25 µg/ml) inhibited production of IL-6 (maximum 70-80%; p≤0.0002) and PGE2 (maximum ~ 60%; p≤0.04). Conclusions: Lack of toxicity of low NDM concentrations to gingival epithelial cells in vitro, and its inhibition of the pro-inflammatory, catabolic mediators PGE2 and IL-6, suggest that cranberry components may regulate oral inflammatory responses and may be useful in prevention or treatment of gingivitis and/or periodontitis. (Supported by UT College of Dentistry Alumni Endowment Fund).