Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation
1 Department of Periodontology, Dental School, University of Seville, c/Avicena s/n, Sevilla, 41009, Spain
2 Departamento de Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Avenida Sanchez Pizjuan s/n, Sevilla, 41009, Spain
3 Department of Physiology, Institute of Nutrition and Food Technology 'José Mataix', Biomedical Research Center, University of Granada, Avenida del Conocimiento s/n, Armilla Granada, 18100, Spain
4 Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Biomedical Research Center, University of Granada, Avenida del Conocimiento s/n, Armilla Granada, 18100, Spain
5 Dipartimento di Scienze Biomediche e Sanità Pubblica - Sezione di Anatomia Patologica Università, Università Politecnica delle Marche, Via Tronto, 10, Ancona, 60100, Italia
6 Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche - Sezione Biochimica, Università Politecnica delle Marche, Via Ranieri, 65, Ancona, 60100, Italia
Citation and License
BMC Medicine 2012, 10:122 doi:10.1186/1741-7015-10-122Published: 17 October 2012
Periodontitis, 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.
Peripheral 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.
We 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.
Results 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.