Inhibition of interleukin‐17‐stimulated interleukin‐6 and ‐8 production by cranberry components in human gingival fibroblasts and epithelial cells

Abstract

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.

Effect of glycated albumin and cranberry components on interleukin‐6 and matrix metalloproteinase‐3 production by human gingival fibroblasts

“…Short‐term exposure to G‐HSA or HSA caused no significant cytotoxic membrane damage resulting in LDH release (data not shown). In addition, our previous studies showed that NDM (≤ 500 μg/mL) and LPS (1 μg/mL), to which the cells were also exposed, caused no significant membrane damage to gingival fibroblasts . While neither G‐HSA nor HSA decreased cell viability, after 3 d exposure all G‐HSA concentrations increased MTT assay values by ~20–30% compared to control, but these values had returned to control level by day 6 (data not shown).…”

“…While neither G‐HSA nor HSA decreased cell viability, after 3 d exposure all G‐HSA concentrations increased MTT assay values by ~20–30% compared to control, but these values had returned to control level by day 6 (data not shown). Furthermore, exposure of the fibroblasts to NDM concentrations ≤ 100 μg/mL for as long as 6 d had no significant effect on cell viability, but after 6 d exposure 250 μg/mL significantly decreased viability by ~40%, and 500 μg/mL caused ~80% decrease (IC50 ≅275 μg/mL at 144 h) . P.g .…”

“…LPS‐stimulated IL‐6 production in normal human gingival fibroblasts and human gingival epithelial cells ( (D. Tipton, N. Zacharia, S. Rawal, M. Dabbous, unpublished studies), and it inhibited IL‐6 production by Aggregatibacter actinomycetemcomitans LPS‐stimulated human gingival fibroblasts . NDM inhibits activation of NF‐κB and MAPK/AP‐1 signaling pathways stimulated by G‐HSA, LPS, IL‐1 and other mediators, resulting in decreased expression of IL‐6 . MMP‐3 production is also under the regulation of NF‐κB and AP‐1 , and although not specifically determined in this study, the inhibition of IL‐6 and MMP‐3 production in the presence of LPS or AGE‐HSA may occur via a similar mechanism.…”

“…The focus of this study was the cranberry ( Vaccinium macrocarpon ), which, like other berry fruits, contain polyphenols, particularly proanthocyanidins, with antioxidant and anti‐inflammatory activities . While several inflammatory cytokines and MMPs such as MMP‐1 have important roles in periodontitis, we chose IL‐6 and MMP‐3 for this study for the reasons cited above and because our studies and those of others have shown that proanthocyanidin‐enriched cranberry preparations can inhibit IL‐6 and MMP‐3 production by gingival fibroblasts and epithelial cells stimulated with LPS, IL‐1β or IL‐17 . The purpose of this study was to investigate the effects of glycated human serum albumin (HSA) and periodontopathogen LPS on gingival fibroblast production of IL‐6 and MMP‐3, and modulation of this response by cranberry components.…”

The presence, function and regulation of IL‐17 and Th17 cells in periodontitis

“…Expression of IL-17 receptors A and C (IL-17RA and IL-17RC) has been shown on gingival epithelium cells, gingival fibroblasts and PDL fibroblasts (Hosokawa et al 2009b, Takahashi et al 2011, Zhu et al 2011. The receptor expression is functional as IL-17 stimulation induced production of IL-6, IL-8/ CXCL8, CCL20, pro-MMP1 and MMP3 by human gingival fibroblasts (Takahashi et al 2005, Beklen et al 2007, Hosokawa et al 2009b, Konermann et al 2011, Tipton et al 2013; and IL-1b, IL-6 and IL-8/CXCL8 production by gingival epithelial cells (Takahashi et al 2011, Tipton et al 2013. Stimulation with IL-17 in combination with other cytokines, such as IFN-c, TNF-a or IL-22 enhanced the pro-inflammatory cytokine production by these stromal cells (Beklen et al 2007, Mahanonda et al 2008, Hosokawa et al 2009a).…”