College of Dentistry, The University of Tennessee Health Science Center, Memphis, TN, USA; Department of Bioscience Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
J Periodontal Res. 2013 Oct;48(5):638-46. doi: 10.1111/jre.12050. Epub 2013 Feb 27.
Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, a product of T-helper 17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins, which have antioxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of lipopolysaccharide-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. The objectives were to determine the effects of IL-17 ± cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.
Cranberry high molecular weight non-dialyzable material (NDM), which is rich in proanthocyanidins, was derived from cranberry juice. Human gingival epithelial cells and normal human gingival fibroblasts were incubated with NDM (5-50 μg/mL), IL-17 (0.5-100 ng/mL), or NDM + IL-17 in serum-free medium for 6 d. IL-6 and IL-8 in culture supernatants were measured by ELISA. Membrane damage and viability were assessed by lactate dehydrogenase activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.
In both cell lines, IL-17 (≥ ~5-10 ng/mL) significantly stimulated production of IL-6 (p < 0.005) and IL-8 (p < 0.03). Non-toxic levels of NDM inhibited constitutive IL-6 and IL-8 production by epithelial cells (p ≤ 0.01) and fibroblasts (p ≤ 0.03) as well as IL-17-stimulated cytokine production by epithelial cells [IL-6 (maximum ~80% inhibition; p ≤ 0.0001); IL-8 (maximum ~70% inhibition; p ≤ 0.03)] and fibroblasts [IL-6 (maximum ~90% inhibition; p ≤ 0.0001); IL-8 (maximum ~80% inhibition; p ≤ 0.008)].
Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by gingival fibroblasts and epithelial cells suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis.
牙龈上皮细胞和成纤维细胞参与牙周炎症和破坏，产生白细胞介素（IL）-6，一种调节破骨细胞骨吸收的调节剂，以及中性粒细胞趋化因子 IL-8。IL-17，一种辅助性 T 细胞 17 细胞的产物，可能通过刺激牙龈细胞产生细胞因子而在牙周炎中发挥作用。蔓越莓（Vaccinium macrocarpon）富含多酚，特别是原花青素，具有抗氧化和其他有益特性。蔓越莓成分可抑制脂多糖刺激的人巨噬细胞、牙龈成纤维细胞和上皮细胞的促炎活性，但对其对 IL-17 刺激的细胞因子产生的影响知之甚少。目的是确定 IL-17 ± 蔓越莓成分对人牙龈上皮细胞和成纤维细胞产生 IL-6 和 IL-8 的影响。
蔓越莓高分子量不可透析物质（NDM）富含原花青素，源自蔓越莓汁。用人牙龈上皮细胞和正常人类牙龈成纤维细胞在无血清培养基中用 NDM（5-50 μg/mL）、IL-17（0.5-100 ng/mL）或 NDM+IL-17 孵育 6 天。通过 ELISA 测量培养上清液中的 IL-6 和 IL-8。通过乳酸脱氢酶释放到细胞上清液中的活性和线粒体酶的活性分别评估膜损伤和细胞活力。使用方差分析和 Scheffe 的 F 程序进行事后比较来分析数据。
在两种细胞系中，IL-17（≥5-10 ng/mL）均显著刺激 IL-6（p<0.005）和 IL-8（p<0.03）的产生。非毒性水平的 NDM 抑制上皮细胞（p≤0.01）和成纤维细胞（p≤0.03）的基础 IL-6 和 IL-8 产生以及上皮细胞[IL-6（最大80%抑制；p≤0.0001）；IL-8（最大70%抑制；p≤0.03）]和成纤维细胞[IL-6（最大90%抑制；p≤0.0001）；IL-8（最大~80%抑制；p≤0.008）]中 IL-17 刺激的细胞因子产生。
蔓越莓 NDM 抑制牙龈成纤维细胞和上皮细胞的基础和 IL-17 刺激的 IL-6 和 IL-8 产生表明，蔓越莓成分可用作宿主调节治疗剂，以预防或治疗牙周炎。
