Interleukin Expression and Activation of Inflammatory/Apoptosis Pathways on Human Gingival Fibroblasts Exposed to...

This in vitro study aimed to analyze the activation of the NFκB p65/MyD88/NALP3 inflammatory pathway and the expression of the BCL-2/BAX/Caspase-3 apoptosis pathway on human gingival fibroblasts (hGFs) after 24 h and 1-week exposure to the eluates of three light-cured commercial composites (GR: GrandioSO, VOCO; BF: Enamel Plus HRi Biofunction, Micerium; FU: Filtek universal restorative, 3M) and the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). A total of 50 light-cured disk-shaped specimens for each composite group (GR, BF and FU) were produced. The tested materials differed in resin matrix composition; notably, GR contained Bis-GMA, whereas BF and FU contained urethane-based dimethacrylates. The hGFs were exposed for 24 h and 1 week to eluates of each group. Pathway activation was evaluated by cell metabolic activity, immunofluorescence analysis and real-time PCR. Inflammatory effects were assessed in hGF culture by measuring proinflammatory cytokine production (ELISA). GR, BF and FU showed a reduction in metabolic activity in a time-dependent manner. GR showed a significant decrease in terms of cell viability after 1 week of exposure and a greater expression of proapoptotic markers than BF and FU. High levels of proinflammatory cytokines were measured after 1 week of culture for GR. The inflammatory pathway was activated in a time-dependent manner. Pathway activation was material-dependent; among the tested composites, GR was found to be more cytotoxic than BF and FU. Despite the limitations of an in vitro study, these findings suggest that dental composite eluates cause time- and material-dependent cytotoxicity, inflammation, and apoptosis in hGFs. Exposure significantly impairs cellular metabolic activity from 24 h up to 1 week. Among the evaluated materials, the GR composite triggered a markedly severe inflammatory and apoptotic effect compared to BF or FU. Ultimately, these findings underscore the potential clinical importance of selecting materials with optimal biocompatibility to minimize adverse tissue reactions, although their direct translation into clinical practice would require further research.