prostaglandin-d2 and Periodontitis

The 15-deoxy-(Δ12,14)-PG J(2) (15d-PGJ(2)) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nanotechnological formulation as a carrier for 15d-PGJ(2), and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D,L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ(2). BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 μg/kg 15d-PGJ(2)-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ(2)-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 μg/kg 15d-PGJ(2)-NC had a reduction of CD4(+)CD25(+)FOXP3(+) cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 μg/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 μg/kg 15d-PGJ(2)-NC, and high amounts of 15d-PGJ(2) were observed in the gingiva. In conclusion, the 15d-PGJ(2)-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model.

Topics: Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Resorption; Disease Models, Animal; Gingiva; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Nanocapsules; Periodontitis; Prostaglandin D2

This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with [14C]arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2 (P less than 0.01), PGD2 (P less than 0.05), and PGA2 (P less than 0.001). Some unidentified metabolites, possibly lipoxygenase products were detected in significantly (P less than 0.001) larger amounts in inflamed than in normal tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Carbon Radioisotopes; Dinoprost; Dinoprostone; Gingiva; Gingivitis; Humans; Periodontitis; Prostaglandin D2; Prostaglandins; Prostaglandins A; Prostaglandins D; Prostaglandins E; Prostaglandins F; Thromboxane B2