A Sequential Micro-Immunotherapy Medicine Increases Collagen Deposition in Human Gingival Fibroblasts and in an Engineered 3D Gingival Model under Inflammatory Conditions

Ferrá-Cañellas, Maria Del MarMunar-Bestard, MartaFloris, IlariaRamis, Joana MariaMonjo, MartaGarcia-Sureda, Laura2024-10-092024-10-092023-06-22Ferrá-Cañellas M del M, Munar-Bestard M, Floris I, Ramis JM, Monjo M, Garcia-Sureda L. A Sequential Micro-Immunotherapy Medicine Increases Collagen Deposition in Human Gingival Fibroblasts and in an Engineered 3D Gingival Model under Inflammatory Conditions. Int J Mol Sci. 2023 Jun 22;24(13):10484.https://hdl.handle.net/20.500.13003/19337https://hdl.handle.net/20.500.12105/23576Periodontal therapies use immune mediators, but their side effects can increase with dosage. Micro-immunotherapy (MI) is a promising alternative that employs immune regulators at low and ultralow doses to minimize adverse effects. In this study, the effects of 5 capsules and the entire 10-capsule sequence of the sequential MI medicine (MIM-seq) were tested in two in vitro models of periodontitis. Firstly, human gingival fibroblasts (hGFs) exposed to interleukin (IL)-1β to induce inflammation were treated with five different capsules of MIM-seq for 3 days or with MIM-seq for 24 days. Subsequently, MIM-seq was analyzed in a 3D model of human tissue equivalent of gingiva (GTE) under the same inflammatory stimulus. Simultaneously, a non-IL-1β-treated control and a vehicle were included. The effects of the treatments on cytotoxicity, collagen deposition, and the secreted levels of IL-1α, IL-6, prostaglandin E2 (PGE2), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were evaluated. None of the tested items were cytotoxic. The complete sequence of MIM-seq decreased PGE2 release and restored collagen deposition levels induced by IL-1β treatment in hGFs exposed to IL-1β. MIM-seq treatment restored collagen production levels in both models. These promising preclinical findings suggest that MIM-seq should be further investigated for periodontitis treatment.enghttp://creativecommons.org/licenses/by/4.0/CollagenImmunotherapyPeriodontitisFibroblastsHumansDinoprostoneCapsulesCells, CulturedGingivaA Sequential Micro-Immunotherapy Medicine Increases Collagen Deposition in Human Gingival Fibroblasts and in an Engineered 3D Gingival Model under Inflammatory Conditionsresearch articleAtribución 4.0 Internacional37445663241310.3390/ijms2413104841422-0067International journal of molecular sciencesopen accessDinoprostonaHumanosCápsulasFibroblastosCélulas CultivadasColágenoInmunoterapiaEncíaPeriodontitis2-s2.0-851648429161031181500001L2024462910