Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation

Abstract

BackgroundPeriodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis.MethodsPeripheral blood mononuclear cells from patients with periodontitis (n = 38) and without periodontitis (n = 20) were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy.ResultsWe found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12) and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy.ConclusionResults from the present study suggest that autophagy is an important and shared mechanism in other conditions related to inflammation or alterations of the immune system, such as periodontitis.

Lipophilic antioxidants prevent lipopolysaccharide-induced mitochondrial dysfunction through mitochondrial biogenesis improvement

“…Furthermore, kidney, brain and liver contain the highest endogenous levels of CoQ 10 [14]. The findings of the present study show that lipophilic antioxidants such as CoQ 10 and vitamin E ameliorated mitochondrial dysfunction, oxidative stress and reduced cell death with a more specific interaction with mitochondrial biogenesis, which is not observed in hydrophilic antioxidants such as NAC or BHA. Since CoQ 10 is a pivotal element in mitochondrial respiratory chain and, at the same time, is an important antioxidant, these results suggest that mitochondrial dysfunction is crucial in the pathophysiology of periodontal disease and CoQ 10 could be a therapeutic option in bacterial LPS infection, sepsis or other similar conditions.…”

“…For this, mitochondrial biogenesis and mitophagy are two pathways that regulate mitochondrial content and metabolism preserving homeostasis. Recently, we described reduced levels of CoQ 10 and mitochondrial chain complex induced by LPS [2] and active autophagic processes in blood cells from periodontitis patients and activated in fibroblasts after P. gingivalis LPS [10]. To assess the functional consequences of decreased respiratory chain enzyme activities and CoQ 10 levels, we determined ATP levels as an indicator of cellular bioenergetics and well-being status.…”

Longitudinal Relationship Between Metabolic Syndrome and Periodontal Disease Among Japanese Adults Aged ≥70 Years: The Niigata Study

“…It is postulated that selective autophagy of mitochondria, known as mitophagy, contributes to the maintenance of mitochondrial quality by eliminating dysfunctional or damaged mitochondria 38 . Oxidative stress has been shown to induce autophagy, 38 and a recent study demonstrated an enhancement of autophagy mediated by mitochondrial ROS in peripheral blood mononuclear cells from patients with periodontal disease 39 . This also supports the hypothesis that mitochondrial function is essential in inflammation‐related disease, including periodontal disease.…”

Community-wide transcriptome of the oral microbiome in subjects with and without periodontitis

“…The production of these molecules by the accompanying community may facilitate iron acquisition by the 'red-complex. ' Finally, genes involved in stress tolerance were highly over-represented in a large fraction of the community and their upregulation may be related to the production of reactive oxygen species during disease (Wright et al, 2011;Bullon et al, 2012).…”