Role of IL-6 and STAT3 signaling in dihydropyridine-induced gingival overgrowth fibroblasts.

OBJECTIVES: This study analyzed the role of the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) pathway in dihydropyridine-induced gingival overgrowth (DIGO) fibroblasts. MATERIALS AND METHODS: Tissue samples were obtained through surgical dissection from five DIGO patients and five healthy individuals. Cell cultures were conditioned with nifedipine (Nif) (0.34 µM) and stimulated with IL-1ß (10 ng/ml) to clarify whether IL-6 upregulates extracellular matrix overproduction or has an impact on the cell proliferation rate of DIGO fibroblasts. STAT3 was knocked down using short hairpin (sh)RNA to determine its role in collagen (Col) type I alpha 1 (Colα1(I)) synthesis. RESULTS: Results showed that phosphorylated (p)STAT3 nuclear translocation was activated by a simulated autocrine concentration (50 ng/ml) of IL-6, and application of an anti-IL-6 antibody significantly decreased the pSTAT3/STAT3 ratio in DIGO fibroblasts. STAT3 knockdown significantly decreased STAT3 and Colα1(I) expressions in DIGO cells. DIGO tissues presented stronger proliferating cell nuclear antigen (PCNA) expression than did healthy individuals under the effect of IL-1ß/Nif treatment. CONCLUSIONS: Gingival inflammation (e.g., IL-1ß) and taking dihydropyridine (e.g., Nif) may additively stimulate Col overproduction through the IL-6-STAT3-Colα1(I) cascade in DIGO cells. IL-6-STAT3 signaling may be considered a target for the control of DIGO.

Antimicrobial agent chloroxylenol targets ß­catenin­mediated Wnt signaling and exerts anticancer activity in colorectal cancer.

Chloroxylenol is the active ingredient of the antibacterial agent Dettol. The anticancer effect and underlying mechanisms of this compound and other common antimicrobial agents have not been clearly elucidated. In the present study, the effects of chloroxylenol, benzalkonium chloride, benzethonium chloride, triclosan and triclocarban on ß­catenin­mediated Wnt signaling in colorectal cancer were evaluated using the SuperTOPFlash reporter assay. It was demonstrated that chloroxylenol, but not the other antimicrobial agents tested, inhibited the Wnt/ß­catenin signaling pathway by decreasing the nuclear translocation of ß­catenin and disrupting ß­catenin/T­cell factor 4 complex, which resulted in the downregulation of the Wnt target genes Axin2, Survivin and Leucine­rich G protein­coupled receptor­5. Chloroxylenol effectively inhibited the viability, proliferation, migration and invasion, and sphere formation, and induced apoptosis in HCT116 and SW480 cells. Notably, chloroxylenol attenuated the growth of colorectal cancer in the MC38 cell xenograft model and inhibited organoid formation by the patient­derived cells. Chloroxylenol also demonstrated inhibitory effects on the stemness of colorectal cancer cells. The results of the present study demonstrated that chloroxylenol could exert anti­tumor activities in colorectal cancer by targeting the Wnt/ß­catenin signaling pathway, which provided an insight into its therapeutic potential as an anticancer agent.

Measurement of gp130 cytokines oncostatin M and IL-6 in gingival crevicular fluid of patients with chronic periodontitis.

Several proinflammatory cytokines can induce periodontal tissue destruction and are thought to be useful indicators or diagnostic markers for periodontitis. Here, we aimed to investigate whether oncostatin M (OSM) was present in gingival crevicular fluid (GCF) and to clarify the correlation of GCF OSM and interleukin-6 (IL-6) levels with the severity of periodontitis. Sixty-two sites in 14 patients were divided into 4 groups based on probing depth (PD) and bleeding on probing (BOP). GCF was collected using paper strips from clinically health sites (PD < or = 3 mm, CAL: 1-3 mm, without BOP, n = 31), mildly diseased sites (PD < or = 3 mm, CAL: 3-5 mm, with BOP, n = 11), moderately diseased sites (PD = 4-6 mm, CAL: 5-8 mm, with BOP, n = 11), and severely diseased sites (PD > 6 mm, CAL: 8-12 mm, with BOP, n = 9). IL-6 and OSM in GCF were quantified by enzyme-linked immunosorbent assay and are expressed as concentrations (pg/ml) and total amounts (pg/site). Correlations of OSM and IL-6 levels with the severity of periodontitis in all groups were determined using Spearman rank correlation (r(s)). Our results showed that OSM and IL-6 were detected in most GCF samples. The total amounts of OSM and IL-6 were significantly positive correlated with severity of diseased sites (OSM: r(s) = 0.526, p < 0.01; IL-6: r(s) = 0.729, p < 0.01). No correlations of OSM or IL-6 concentration in GCF were found with disease severity. OSM and IL-6 levels in GCF were positively correlated to each other when expressed as either concentrations or total amounts (concentrations: r = 0.485, p < 0.01; total amounts r = 0.490, p < 0.01). In conclusion, our findings suggest that IL-6 and OSM may play a role in modulating the inflammatory cascade of chronic periodontitis.