Presence of markers of activation pathways of macrophages in chronic periodontitis

Indexación: Web of Science; ScieloLa periodontitis crónica es una patología infecciosa, causada por un complejo de especies bacterianas, que afecta principalmente los tejidos de inserción de los dientes. La respuesta inmune-inflamatoria producida se caracteriza por la presencia de un infiltrado inflamatorio, en el cual los macrófagos representan entre 5 al 30%. Es sabido que los macrófagos se activan mediante dos vías: Clásica y Alterna, caracterizadas por la presencia de marcadores indirectos: IFN-γ e IL-6 para la vía clásica e IL-4 para la vía alterna, ampliamente abordados. Recientemente, se ha descrito a la subunidad A del factor XIII de la coagulación (FXIII-A) como un buen marcador de la vía alterna. El objetivo de este estudio consiste en determinar la presencia de IFN-γ, IL-6, FXIII-A e IL-4 como marcadores de las vías de activación de los macrófagos, en pacientes con periodontitis crónica. Para tal efecto, se realizó inmunohistoquímica y Western-Blot para los cuatro marcadores junto a CD-68, marcador de macrófagos, en 18 biopsias de tejido periodontal sano y 18 con periodontitis crónica. Se detectó la presencia de IFN-γ, IL-6, IL-4 y FXIII-A junto a CD68+, en todas las muestras de pacientes sanos y con periodontitis. Los resultados obtenidos sugieren que al estar presente IFN-γ, IL-6, IL-4 y FXIII-A, los macrófagos se activarían a través de ambas vías, lo cual, produciría una respuesta tanto proinflamatoria (Th1) como antinflamatoria (Th2). Son necesarios más estudios para determinar si existe una vía preferencial de activación.Periodontitis is a chronic infectious disease caused by a bacterial species complex, which affects mainly the insertion tissues of the teeth. The immune-inflammatory response produced is characterized by an inflammatory infiltrate in which macrophages represent between 5 to 30%. It is known and has been widely discussed that macrophages are activated in two ways: Classical and Alterna, characterized by the presence of indirect markers: IFN-γ and IL-6 for the classical pathway and IL-4 for the alternative pathway. Recently the subunit A of the clotting factor XIII (FXIII-A) has been described as a good marker of the alternative pathway. The objective of this study is to determine the presence of IFN-γ, IL-6, IL-4 and FXIII-A as markers of the macrophage activation pathways in patients with chronic periodontitis. To this end, we performed immunohistochemistry and Western blot for the four markers with CD68 macrophage marker, in 18 healthy periodontal tissue biopsies and 18 with chronic periodontitis. We detected the presence of IFN-γ, IL-6, IL-4 and FXIII-A with CD68 +, in all samples of healthy patients and periodontitis. The results suggest that when present, IFN-γ, IL-6, IL-4 and FXIII-A, activate macrophages through both routes, which would produce a proinflammatory response (Th1) as antiinflammatory (Th2). Further studies are necessary to determine whether there is a preferential pathway activation.http://www.scielo.cl/pdf/piro/v5n3/art06.pd

Presencia de Linfocitos T Reguladores en Periodontitis Crónica

ResumenLa enfermedad periodontal requiere de un hospedero susceptible para su desarrollo y progresión. Dentro de las características del hospedero se encuentra la respuesta T reguladora, que otorga tolerancia frente a antígenos propios y participa durante las enfermedades infecciosas limitando el daño tisular, sin disminuir la respuesta antibacteriana. El presente estudio tiene por objetivo determinar la presencia, reclutamiento y función de Tregs en pacientes con periodontitis crónica. En 10 biopsias de tejido periodontal sano y con periodontits crónica se realizó inmunohistoquímica para marcadores (CD4, CD25, Foxp3), quimioquinas (CCL17, CCL22) y citoquinas (TGF-β, IL-10) de Tregs. Además de Western-Blot para detectar las citoquinas. Los resultados obtenidos sugieren una posible asociación entre células Tregs y la infección periodontal, ya que se confirma su reclutamiento y presencia. Sin embargo, son necesarios más estudios del posible desbalance con su contraparte pro-inflamatoria Th17, que expliquen en parte la compleja etiopatogenia de la enfermedad periodontal.AbstractPeriodontal disease requires a susceptible host to initiation, development and progression. T regulatory response is one of these inmunoregulatory characteristics of the susceptible host, which provide tolerance, tissular protection during infection without impairing the control of periodontopathogens. The aim of this study is to determinate the presence, homing and function of T regulatory cells (Tregs) in patients with chronic periodontitis. Ten biopsies were taken from pockets, the presence of Tregs markers (CD4, CD25, Foxp3), chemokines (CCL17, CCL22) and cytokines (TGF-β, IL-10) were determinate by immunohistochemistry. Cytokines also were detected with Western-Blot. Our results suggest a possible association between Tregs and periodontal infection, confirming homing and presence of Tregs. However, further studies are required to determine the possible imbalance with pro-inflammatory part Th17, that might explain the complex etiopathogenesis of periodontal disease

Interleukin-21 expression and its association with proinflammatory cytokines in untreated chronic periodontitis patients

Background: Interleukin-21 (IL-21) controls the differentiation of T-helper Th17 cells and induces the production of IL-17 in this T-cell subtype. The aim of this study is to determine the relative expression of IL-21 in gingival tissues of chronic periodontitis patients and correlate/associate this expression with proinflammatory cytokines and clinical parameters of disease. Methods: Samples of gingival biopsies were collected from chronic periodontitis patients (n = 10) and controls (n = 8). The mRNA expressions of IL-21, IL-1b, IL-6, IL-17, IL-23, IL-10, and transforming growth factor-b1 (TGF-b1) were quantified using real-time reverse transcription-polymerase chain reaction. IL-21 levels were compared between chronic periodontitis and healthy gingival tissues and correlated with cytokine and clinical parameters of tissue destruction. Results: A significant overexpression of IL-21, IL-1b, IL-6, IL-17, and IL-23p19 was detected in periodontal disease– affected tissues compared to healthy gingival tissues. IL-10 and TGF-b1 were, however, downregulated in periodontal lesions. IL-21 yielded significant positive correlations with probing depth, clinical attachment level, IL-1b, and IL-6. In addition, IL-21 was negatively correlated with IL-10 and TGF-b1. Conclusions: IL-21 was overexpressed in chronic periodontitis gingival tissues and correlated with clinical parameters of periodontal destruction and with proinflammatory cytokines. Therefore, IL-21 might play a role in the tissue destruction that characterizes chronic periodontal disease. J Periodontol 2012;83:948-954

Diagnostic accuracy for apical and chronic periodontitis biomarkers in gingival crevicular fluid: an exploratory study

AIM: The aim of this study was to assess the levels and diagnostic accuracy of a set of potential biomarkers of periodontal tissue metabolism in gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and asymptomatic apical periodontitis ( AAP). MATERIALS AND METHODS: Thirty one GCF samples from 11 CP patients, 44 GCF samples from 38 AAP patients and 31 GCF samples from 13 healthy volunteers were obtained (N = 106). Matrix metalloproteinases (MMPs) -2 and -9 were determined by zymography; levels of MMP-8 by ELISA and IFMA and MPO by ELISA. IL-1, IL-6, TNFα, DKK-1, Osteonectin, Periostin, TRAP-5 and OPG were determined by a multiplex quantitative panel. Statistical analysis was performed using linear mixed-effects models. RESULTS: The MMP-9 and MMP-8 were higher in CP, followed by AAP, versus healthy individuals (p 0.97) in CP, and for the active form of MMP-9 and MMP-8 (AUC > 0.90) in AAP. CONCLUSION: Gingival crevicular fluid composition is modified by CP and AAP. MMP-9 and MMP-8 show diagnostic potential for CP and AAP, whereas MMP-2 and TRAP-5 are useful only for CP.status: publishe