Epigenetic Signatures of Salivary Gland Inflammation in Sjögren's Syndrome

This study conducted in SGEC emphasises the role of DNA methylation in pSS pathogenesis and supports the necessity to conduct pure cell analysis for future EWAS studies when analysing salivary glands from patients with pSS.

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.

Oral symptoms are among the most distressing manifestations for patients with Sjögren’s syndrome (SS). The feeling of dry mouth is unpleasant, and hyposalivation may contribute to difficulty in speaking, chewing and swallowing and reduced quality of life. Reduced salivary flow increases the risk for dental caries and problems with prosthetic replacement. It seems that SS is not as frequently occurring as previously anticipated. Population-based prevalence studies on primary SS in Europe, conducted on large background populations and in accordance with the AECG criteria, reported of a prevalence of 1–9 cases per 10,000 people. This gives a combined prevalence of nearly 39/100,000 (~0.04 %). The cause of Sjögren’s syndrome is even now not fully understood, and the treatment of oral symptoms is still mostly palliative. Hopefully, useful information will appear from the new methods that are now available for genome wide association studies, epigenetics, DNA methylation studies, and proteomics. Similarly, this is anticipated for the immunological side of the story. The interferon signature, the interferon γ/interferon α mRNA ratio, and CXCL13 are among the proposed biomarkers of active disease. In this review, we provide an update on oral aspects of Sjögren’s syndrome with emphasis on the latest publications on these topics.