Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

Abstract

MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis. The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-␣] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmumiR-2137 did not modify TNF-␣ secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In P. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-␣ secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a mouse model of P. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine-and chemokinerelated pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of P. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmumiR-2137 to control inflammation induced by P. gingivalis infection.

RETRACTED ARTICLE: The Notch signal mediates macrophage polarization by regulating miR-125a/miR-99b expression

“…It has previously been reported that [9,10] a variety of miRNAs can regulate macrophage polarization. In this study, the chip results show that Notch signal knockout can affect the change of miRNA expression profile of macrophages.…”

“…Therefore, the Notch signalling pathway is involved in macrophage polarization regulation. Besides, a variety of miRNAs can regulate macrophage polarization [9,10], and changes of the Notch signalling pathway can significantly alter the expressions of miR-125a and miR-99b. Thereby motivated, we herein aimed to clarify the molecular mechanism by which the Notch signalling pathway regulated miR-125a/miR-99b expression to mediate macrophage polarization.…”

Differential Brain MicroRNA Expression Profiles After Acute and Chronic Infection of Mice With Toxoplasma gondii Oocysts

“…The top 10 most differentially abundant miRNAs in chronic infection, as shown in Table 3 , were the most overexpressed (3–4-fold increase) in chronic infection. The mmu-miR-155-5p was shown to be abundantly expressed in immune cells involved in mouse inflammatory responses, through inhibiting SOCS1 to enhance IFN-α ( Rao et al, 2014 ) and decrease TNF-α ( Huck et al, 2017 ). Also, the upregulation of mmu-miR-146a-5p is relevant to myeloid cell proliferation, inflammation and cancer ( Boldin et al, 2011 ).…”

Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model

“…Several underlying mechanisms contributing to the association between PD and RA have been identified, highlighting a role for bacterial recognition and activation of inflammatory pathways leading to cytokine secretion. P. gingivalis is able to directly activate several cell types, including macrophages, fibroblasts, or chondrocytes, contributing to the sustained inflammation and cartilage destruction (21,28,29). For instance, modulation of TLR-2 and -4 mediates the inflammatory response to P. gingivalis expression (30), leading to an increase of TNF-␣, IL-1, IL-6, or IL-17 at the RA lesion site (31).…”