Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels of proteolytic activity (arginine cleavage) compared to asymptomatic controls. This was dependent on the activation of NF-κB. In addition, increased proteolytic activity was measured in vivo, in colonic washes from IBS compared with control patients. Trypsin and tryptase expression and release were increased in colonic biopsies from IBS patients compared with control subjects. Biopsies from IBS patients (but not controls) released mediators that sensitized murine sensory neurons in culture. Sensitization was prevented by a serine protease inhibitor and was absent in neurons lacking functional protease-activated receptor-2 (PAR 2 ). Supernatants from colonic biopsies of IBS patients, but not controls, also caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon. These pronociceptive effects were inhibited by serine protease inhibitors and a PAR 2 antagonist and were absent in PAR 2 -deficient mice. Our study establishes that proteases are released in IBS and that they can directly stimulate sensory neurons and generate hypersensitivity symptoms through the activation of PAR 2 .

These data provide evidence that systemic therapy with celecoxib can modify the progression of experimentally induced periodontitis in rats.

Background and Objective Although previous studies revealed the potential use of probiotics in the control of periodontitis, little is known about their interactions with gingival epithelial cells (GECs). Since GECs comprise the first defense in the subgingival microenvironment, the aim of this study was to evaluate the effect of probiotic lactobacilli and bifidobacteria strains on OBA‐9 cells challenged with Porphyromonas gingivalis. Methods Immortalized human GECs (OBA‐9) were challenged with live P. gingivalis (strains W83 and ATCC33277) and co‐infected with one of 12 tested probiotic strains at a multiplicity of infection (MOI) of 1:1000 for 2 hours. Bacterial adhesion and invasion were determined by antibiotic exclusion analysis and CFU counting. OBA‐9 viability was assessed by MTT assay, and levels of inflammatory mediators (TNF‐α, IL‐1β, and CXCL8) in the supernatants were determined by ELISA. The expression of genes encoding Toll‐like receptors (TLR2, TLR4) was evaluated by RT‐qPCR. Results Both strains of P. gingivalis were able to adhere and invade OBA‐9 cells, with significant loss in cell viability, increase in the levels of TNF‐α and IL‐1β, and upregulation of TLR4. However, co‐infection with probiotics attenuated these effects in P. gingivalis challenged GECs. Most probiotics maintained OBA‐9 viability and reduced pathogens adhesion and invasion. Furthermore, probiotics were able to adhere to GECs, which was enhanced for most strains in the presence of P. gingivalis. The synthesis of IL‐1β and TNF‐α by P. gingivalis in challenged GECs was reduced in co‐culture with most of the tested probiotics, whereas the secretion of CXCL8 increased, and TLR4 was downregulated. Conclusion Probiotics can alter the interaction of GECs with P. gingivalis by modulating the pathogen's ability to adhere and invade these cells, as well as by regulating the innate immune response. Such properties are strain‐specific and may indicate the most efficient probiotics to control periodontitis.

Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PAR2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR2 activation may participate in periodontal disease in vivo. We investigated the role of PAR2 activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR2 agonist causes periodontitis but also exacerbates existing periodontitis, leading to significant alveolar bone loss and gingival granulocyte infiltration. Inhibition of matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) decreased PAR2 agonist-induced periodontitis. More specifically, the overexpression of COX-1, COX-2, MMP-2, and MMP-9 in gingival tissues suggests that they are involved in PAR2-induced periodontitis. In conclusion, PAR2 agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR2 may represent a novel approach to modulate host response in periodontitis.

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The data from the present study suggest that long-term administration of cyclosporin A may negatively influence bone healing around dental implants.

Within the limits of this study, it can be suggested that the severity of periodontal disease was not affected by short-term diabetes, and that experimental periodontitis increased blood glucose levels in uncontrolled diabetic rats.

These data provide evidence that systemic therapy with etoricoxib can retard alveolar bone loss in a ligature-induced periodontitis model in rats.