RESUMEN

Molecular mechanisms responsible for periodontal disease (PD) and its worsening in type 1 Diabetes Mellitus (DM1) remain unknown. Cytokine profile and expression levels of collagenases, Mmp14, and tissue inhibitors were determined, as were the numbers of neutrophils and macrophages in combined streptozotocin-induced DM1 and ligature-induced PD models. Increased IL-23 (80-fold) and Mmp8 expression (25-fold) was found in DM1. Ligature resulted in an IL-1ß/IL-6 profile, increased expression of Mmp8, Mmp13, and Mmp14 (but not Mmp1), and transient expression of Timp1 and Reck in non-diabetics. PD in DM1 involved IL-1ß (but not IL-6) and IL-23/IL-17, reduced IL-6 and IL-10, sustained Mmp8 and Mmp14, increased Mmp13 and reduced Reck expression in association with 20-fold higher counts of neutrophils and macrophages. IL-23 and Mmp8 expression are hallmarks of DM1. In association with the IL-1/IL-6 (Th1) response in PD, one found a secondary IL-17 (Th17) pathway in non-diabetic rats. Low IL-6/TNF-α suggest that the Th1 response was compromised in DM1, while IL-17 indicates a prevalence of the Th17 pathway, resulting in high neutrophil recruitment. Mmp8, Mmp13, and Mmp14 expression seems important in the tissue destruction during PD in DM1. PD-associated IL-1/IL-6 (Th1), IL-10, and Reck expression are associated with the acute-to-chronic inflammation transition, which is lost in DM1. In conclusion, IL-23/IL-17 are associated with the PD progression in DM1.

Asunto(s)

Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Encía/enzimología , Encía/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Metaloproteinasa 14 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Enfermedades Periodontales/complicaciones , Pérdida de Hueso Alveolar/enzimología , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/inmunología , Animales , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/enzimología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Progresión de la Enfermedad , Proteínas Ligadas a GPI/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ligadura , Macrófagos/inmunología , Masculino , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 14 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/genética , Diente Molar/cirugía , Infiltración Neutrófila , Neutrófilos/inmunología , Enfermedades Periodontales/enzimología , Enfermedades Periodontales/genética , Enfermedades Periodontales/inmunología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Células Th17/inmunología , Factores de Tiempo , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia Arriba