The negative feedback regulation of microRNA-146a in human periodontal ligament cells after Porphyromonas gingivalis lipopolysaccharide stimulation

Jiang, Shiwei; Dong, Xue; Xie, Yufeng; Zhu, Dongwang; Dong, Yunyun; Wei, Changjiang; Deng, Jiayin

doi:10.1007/s00011-015-0824-y

Cited by 36 publications

(47 citation statements)

References 36 publications

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“…According to our previous study [10, 11], P. gingivalis LPS activated the Toll-like receptor-nuclear factor (NF)-κB signaling pathway. Based on the information, we found two key factors, IRAK1 and TRAF6, which were candidate targets of miR-146a involved in this pathway.…”

Section: Resultsmentioning

confidence: 99%

“…It has been demonstrated that miRs function as an important regulator in periodontitis [8, 9]. Our previous studies demonstrated that miR-146a regulated the cytokine secretion in human gingival fibroblasts and periodontal ligament cells [10, 11]. Recent studies from others delineated that miR-128 controlled the inflammatory response in macrophages after stimulated with porphyromonas gingivalis ( P. gingivalis) [12], and miR-24 acted as a negative regulator in the polarization and plasticity of macrophages activated by P. gingivalis LPS or A. actinomycetemcomitans LPS [13].…”

Section: Introductionmentioning

confidence: 99%

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miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6

Jiang

Deng

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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It has been suggested that microRNAs (miRs) are involved in the immune regulation of periodontitis. However, it is unclear whether and how miRs regulate the function of B cells in the context of periodontitis. This study is to explore the role of miR-146a on the inflammatory cytokine production of B cells challenged by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). Primary B cells were harvested from mouse spleen. Quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of inflammatory cytokines in B cells in the presence or absence of P. gingivalis LPS and/or miR-146a. Bioinformatics, luciferase reporter assay and overexpression assay were used to explore the binding target of miR-146a. Our results showed that miR-146a level in B cells was elevated by P. gingivalis LPS stimulation, and the mRNA expressions of interleukin (IL)-1β, 6 and 10, and IL-1 receptor associated kinase-1 (IRAK1), but not TNF receptor associated factor 6 (TRAF6), were also upregulated. The expression levels of IL-1β, 6, 10 and IRAK1 were reduced in the presence of miR-146a mimic, but were elevated by the addition of miR-146a inhibitor. MiR-146a could bind with IRAK1 3' untranslated region (UTR) but not TRAF6 3'-UTR. Overexpression of IRAK1 reversed the inhibitory effects of miR-146a on IL-1β, 6 and 10. In summary, miR-146a inhibits inflammatory cytokine production in B cells through directly targeting IRAK1, suggesting a regulatory role of miR-146a in B cell-mediated periodontal inflammation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6

Jiang

Deng

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…pathways in vitro (25,26) or in vivo (27). Several other pathways have been identified as putative targets of P. gingivalis leading to uncontrolled secretion of cytokines such as SOCS3 (28).…”

Section: Gingivalis (Pg) (A To C) Combination (P Gingivalis and Mirmentioning

confidence: 99%

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

et al. 2017

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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.

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“…Jiang et al [32] reported that P. gingivalis LPS (10 µg/mL) increased the expression of TLR2, TLR4, and miRNA-146a in human periodontal ligament cells (HPDLCs). At 1 µg/mL LPS, P. gingivalis induced TLR2, miRNA-146a, and NF-κB p65 nuclear activity and enhanced cytokine secretion but without affecting TLR4.…”

Section: Possible Functions For Mirna-146 and Mirna-155 In Periodontitismentioning

confidence: 99%

“…At 1 µg/mL LPS, P. gingivalis induced TLR2, miRNA-146a, and NF-κB p65 nuclear activity and enhanced cytokine secretion but without affecting TLR4. However, upregulation of miRNA-146a was inhibitory to both anti-TLR2/4 monoclonal antibodies (mAb) [32]. Rather surprisingly, after blocking with the aforementioned mAbs, miRNA-146a, TLR2, TLR4, NF-κB p65 nuclear activity, and pro-inflammatory cytokines increased.…”

Section: Possible Functions For Mirna-146 and Mirna-155 In Periodontitismentioning

confidence: 99%

Periodontitis, pathogenesis and progression: miRNA-mediated cellular responses toPorphyromonas gingivalis

Olsen

Singhrao

Osmundsen

2017

Journal of Oral Microbiology

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Porphyromonas gingivalis is considered a keystone pathogen in periodontitis, a disease typically driven by dysbiosis of oral inflammophilic polymicrobial pathobionts. To combat infectious agents, the natural defense response of the host is to switch on inflammatory signaling cascades, whereby microRNA (miRNA) species serve as alternative genetic inhibitory transcriptional endpoints. miRNA profiles from diseased sites differ from those detected in disease-free tissues. miRNA profiles could therefore be harnessed as potential diagnostic/prognostic tools. The regulatory role of some miRNA species (miRNA-128, miRNA-146, miRNA-203, and miRNA-584) in the innate immune system suggests these molecular signatures also have potential in therapy. P. gingivalis–associated miRNAs are likely to influence the innate immune response, whereas its lipopolysaccharide may affect the nature of host miRNAs and their mRNA targets. This mini review discusses miRNA-dependent transcriptional and regulatory phenomena ensuing immune signaling cascade switch-on with development and progression of periodontitis initiated by P. gingivalis exposure.

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The negative feedback regulation of microRNA-146a in human periodontal ligament cells after Porphyromonas gingivalis lipopolysaccharide stimulation

Abstract: MiRNA-146a functions as a negative feedback regulator via down-regulating proinflammatory cytokine secretion and blocking TLRs signaling pathway in hPDLCs after P. gingivalis LPS stimulation.

Cited by 36 publications

References 36 publications

miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6

miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6

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

Periodontitis, pathogenesis and progression: miRNA-mediated cellular responses toPorphyromonas gingivalis

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