IADR Abstract Archives
Porphyromonas Gingivalis Modulates miRNA Expression in Macrophages: Potential Therapeutic Interests
Objectives: Micro-RNAs (miRNA) are short, non-coding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Interestingly, potential use as therapeutic agents has been proposed for miRNA in treatment of several inflammatory diseases. However, their role in the regulation of inflammatory response induced by Porphyromonas gingivalis (Pg) in the context of periodontitis was lacking. Therefore, the aim of this study was to evaluate the effects induced by Pg infection in macrophages on miRNAs expression.
Methods: Bone-marrow-derived macrophages (BMMs) were harvested and infected by Pg ATCC 33277 (MOI 25) for 3h. Then the expression of miRNA was evaluated with microarray. Selected differentially expressed miRNAs were transfected in BMMs, for which cytokine secretions (TNF-alpha; IL-10) were measured. A murine calvarial lesion was induced by Pg infection and potential therapeutic interest of the selected miRNAs was evaluated at the histological level.
Results: Microarray analysis highlighted several changes regarding miRNAs expression. 8 miRNAs were significantly modulated between control and infected cells (at least 2-fold with p<0,001). Bioinformatic analysis revealed that modulated miRNAs were involved in several inflammatory and immunity related pathways. Mmu-miR-2137 and mmu-miR-155 were selected and transfected in infected BMMs. Anti-miR-2137 increased anti-inflammatory IL-10 secretion while mmu-miR-155 overexpression decreased TNF-alpha secretion. In vivo, injection of anti-miR-2137 concomitantly to Pg reduced inflammatory cell infiltration, osteoclast activity and bone loss, histologically.
Conclusions: This study contributes to demonstrate the effects induced by Pg infection at the miRNAs level. These effects may be considerate as potential mechanisms involved in bacterial survival within host tissues. Some of the differentially expressed miRNAs may be used as potential target to control inflammation at the periodontal level.
Methods: Bone-marrow-derived macrophages (BMMs) were harvested and infected by Pg ATCC 33277 (MOI 25) for 3h. Then the expression of miRNA was evaluated with microarray. Selected differentially expressed miRNAs were transfected in BMMs, for which cytokine secretions (TNF-alpha; IL-10) were measured. A murine calvarial lesion was induced by Pg infection and potential therapeutic interest of the selected miRNAs was evaluated at the histological level.
Results: Microarray analysis highlighted several changes regarding miRNAs expression. 8 miRNAs were significantly modulated between control and infected cells (at least 2-fold with p<0,001). Bioinformatic analysis revealed that modulated miRNAs were involved in several inflammatory and immunity related pathways. Mmu-miR-2137 and mmu-miR-155 were selected and transfected in infected BMMs. Anti-miR-2137 increased anti-inflammatory IL-10 secretion while mmu-miR-155 overexpression decreased TNF-alpha secretion. In vivo, injection of anti-miR-2137 concomitantly to Pg reduced inflammatory cell infiltration, osteoclast activity and bone loss, histologically.
Conclusions: This study contributes to demonstrate the effects induced by Pg infection at the miRNAs level. These effects may be considerate as potential mechanisms involved in bacterial survival within host tissues. Some of the differentially expressed miRNAs may be used as potential target to control inflammation at the periodontal level.