Role of cytokines and inflammatory mediators in tissue destruction

Abstract

Colonization or emergence of microbial pathogens may result in tissue destruction by activation of one or more of five distinct host degradative pathways (matrix metalloproteinase pathway, plasminogen-dependent pathway, phagocytic pathway, PMN-serine proteinase pathway and osteoclastic bone resorption) or by direct cleavage of extracellular matrix constituents by microbial proteinases. Activation of endogenous destructive pathways may be mediated by immune responses resulting in expression of degradative cellular phenotypes among both immigrant and resident cell populations. In addition, expression of degradative phenotypes may be triggered by direct influences on host cells of microbial products (LPS, enzymes, toxins). A body of evidence suggests that each of these mechanisms involves local production of proinflammatory cytokines and growth factors. The matrix metalloproteinase pathway is centrally involved in dissolution of all unmineralized connective tissues and perhaps in resorption of bone as well. The matrix metalloproteinase family consists of nine or more genetically distinct Zn++ endopeptidases which collectively cleave all of the constituents of the extracellular matrix. Recent studies have uncovered many essential elements of a complex, but still incomplete, regulatory network that governs tissue destruction. Proinflammatory cytokines and growth factors induce signalling pathways several of which are dependent on protein kinase C and result in transient expression of the transcription factors c-jun and c-fos. Initiation of transcription of most matrix metalloproteinase genes requires binding of the transcription factor AP-1 (c-jun/c-fos) to a specific promoter sequence but attainment of maximal transcription rates is dependent on interaction with other promoter elements as well. Several matrix metalloproteinases have been detected in crevicular fluids and tissues of inflamed human gingiva as have the proinflammatory cytokines (IL-1 and TNF-alpha) which regulate their transcription. Although the mere presence of enzymes and cytokines does not necessarily impart function per se, these observations suggest that some level of spatial or temporal linkage exists between metalloproteinase/cytokine expression and gingival inflammation.

Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

“…It is generally accepted, however, that the cytokine mediates the osteoclastogenic effect of lipopolysaccharide (5, 39), and we have found that TNF-␣ also mediates the osteoclastogenic activity of CpG-ODN (16). Bacterial products are involved in a variety of pathological bone loss situations in human at least in part because of increased TNF-␣ production (40,41). The pleiotropic cytokine TNF-␣ is involved in a variety of diseases, and it is therefore not surprising that the influence of the cytokine polymorphisms on its production and disease have drawn attention.…”

Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

“…Human periodontal ligament cells play a role in osteoclastogenesis through expression of receptor activator of nuclear factor kappa B ligand (RANKL) on the cell surface in response to exposure to periopathogenic factors and inflammatory cytokines 3) . Studies using bone cell models have demonstrated that formation of osteoclasts requires interaction between nuclear factor kappa B (NF-κB), which is expressed on the surface of osteoclasts, and RANKL in the presence of macrophage colony-stimulating factor (M-CSF) 26) .…”

Mecanismos inmunológicos de las enfermedades periodontales y periimplantarias

“…El papel de las distintas quimioquinas y sus receptores en la migración leucocitaria es defendido por Butcher (7) aunque su implicación en la progresión de la periodontitis es de reciente investigación. Aunque gran número de bacterias son capaces de producir una degradación directa de los tejidos, Birkedal-Hasen y cols (8), sugieren que el tejido conjuntivo del hospedador se degrada principalmente por mecanismos del propio nospedador. La pérdida de tejido conjuntivo representa un mecanismo de defensa del hospedador que intenta protegerse merced a la proliferación del epitelio de unión en su sentido apical (9-10).…”

“…La manifestación de la enfermedad depende de la interacción entre factores del hospedador, ambientales y del agente microbiológico por lo que es probable que un ambiente específico y factores genéticos sean los que puedan en cierto grado determinar la susceptibilidad del individuo (8,11). Por lo tanto la microbiota bacteriana periodontopatógena es necesaria pero no suficiente para que exista enfermedad siendo necesario la presencia de un hospedador susceptible (12).…”