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MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells.

ABSTRACT: MicroRNAs (miRNAs) have been established as key regulators of various biological processes with possible involvement in the pathobiology of periodontal disease. Expanding our earlier observations of substantial differential expression of specific miRNAs between clinically healthy and periodontitis-affected gingival tissues, we used miRNA inhibitors (sponges) in loss-of-function experiments to investigate the involvement of specific miRNAs in the response of pocket epithelium-derived, telomerase-immortalized human gingival keratinocytes (TIGKs) to microbial infection. We constructed stable knockdown (KD) cell lines for five epithelium-expressed miRNAs (miR-126, miR-141, miR-155, miR-210, and miR-1246) and assessed their response to infection with periodontal pathogens using microarray analysis, quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot assay. miR-126 KD cells showed lower expression of interleukin 8 (IL-8) and CXCL1, both on the mRNA and protein levels, than did controls upon stimulation by heat-killed wild-type Porphyromonas gingivalis, live P. gingivalis protease-deficient mutant KDP128, and live Aggregatibacter actinomycetemcomitans In contrast, infection of miR-155 KD and miR-210 KD cells with the same organisms resulted in higher IL-8 and CXCL1 mRNA and protein expression. These effects appeared to be regulated by NF-?B, as suggested by altered transcription and/or phosphorylation status of components of the NF-?B system. Reduced neutrophil-like HL-60 cell chemotactic activity was observed in response to infection of miR-126 KD cells, indicating that miR-126 plays an important role in immune responses. Our findings indicate that specific miRNAs regulate the expression of inflammatory cytokines in human gingival epithelial cells in response to microbial infection.

SUBMITTER: Chen SC

PROVIDER: S-EPMC5116707 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells.

Chen Steven C Y SC Constantinides Christos C Kebschull Moritz M Papapanou Panos N PN

Infection and immunity 20161118 12

MicroRNAs (miRNAs) have been established as key regulators of various biological processes with possible involvement in the pathobiology of periodontal disease. Expanding our earlier observations of substantial differential expression of specific miRNAs between clinically healthy and periodontitis-affected gingival tissues, we used miRNA inhibitors (sponges) in loss-of-function experiments to investigate the involvement of specific miRNAs in the response of pocket epithelium-derived, telomerase- ...[more]

PMID: 27600506

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Project description:The present study explored whether the dopamine 2-like receptor agonist, ropinirole, a drug used for treating Parkinson's disease, suppresses neutrophilic inflammation and alveolar bone loss in an experimental rat model of periodontitis. Periodontitis is a neutrophilic inflammatory disease caused by periodontal pathogens. An excessive T helper (Th)17 immune response is involved in the progression of periodontitis, and interleukin (IL)-17 promotes the exacerbation of inflammation and alveolar bone destruction. Recent evidence has suggested that dopamine signaling plays a key role in Th17 cell differentiation, and that dopamine 2-like receptor agonists suppress cytokine production from Th17 cells. We previously demonstrated that tannic acid, which is a dopamine 2-like receptor agonist, inhibits alveolar bone resorption in an experimental model of periodontitis. The present study used a carrageenan-induced rat model of periodontitis with or without ropinirole. Micro-computed tomography analysis was performed. Cells of the murine gingival epithelial cell line GE1 were stimulated with carrageenan and IL-17A in the presence or absence of ropinirole. The anti-inflammatory effect of ropinirole was analyzed using reverse transcription- quantitative PCR and enzyme-linked immunosorbent assay. Subsequently, in the carrageenan-induced rat model of periodontitis, alveolar bone resorption was observed in the maxillary second molar by micro-computed tomography analysis. Intriguingly, ropinirole suppressed the alveolar bone destruction. The expression levels of C-X-C motif chemokine ligand 1 (CXCL1) and IL-17 receptor A (IL-17RA) in GE1 cells were increased by carrageenan, and CXCL1 expression in GE1 cells was upregulated under IL-17A stimulation. Moreover, ropinirole inhibited CXCL1 and IL-17RA expression in GE1 cells in the presence of IL-17A and carrageenan. Finally, haloperidol promoted CXCL1 expression in GE1 cells in the presence of carrageenan. Overall, these findings suggested that ropinirole suppressed neutrophilic inflammation and alveolar bone destruction in periodontitis by inhibiting CXCL1 expression in gingival epithelial cells through the dopamine 2-like receptor. Thus, ropinirole shows promise as a drug for the treatment of periodontitis.

Dataset Information

MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells.

Publications

MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells.

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