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Prolyl hydroxylase inhibitor DMOG suppressed inflammatory cytokine production in human gingival fibroblasts stimulated with Fusobacterium nucleatum

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Abstract

Objective

Fusobacterium nucleatum (F. nucleatum) is one of the most common bacteria involved in the initiation and progression of periodontal diseases. Pharmacological inhibitor of prolyl hydroxylases (PHDs), dimethyloxallyl glycine (DMOG), has been reported to exert anti-inflammatory effects. The aim of this investigation was to evaluate the role of DMOG in inflammatory cytokine production of human gingival fibroblasts (HGFs) stimulated with F. nucleatum.

Material and methods

HGFs were pretreated with 10, 50, and 100 μM DMOG for 24 h before infected with F. nucleatum (MOI = 100). Cell morphology and survival after infection with F. nucleatum were determined by crystal violet staining assay. The mRNA levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and IL-1β were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The production of IL-6, IL-8, TNF-α, and IL-1β was assessed by enzyme-linked immunosorbent assay (ELISA).

Results

F. nucleatum did not affect the morphology and survival of HGFs by the concentrations of MOI (multiplicity of infection) = 10, 50, and 100. The mRNA levels of IL-6, IL-8, TNF-α, and IL-1β were significantly enhanced with the stimulation of F. nucleatum, and the maximal effect reached at 6 h. The secretion of IL-6, IL-8, and TNF-α was significantly upregulated by the infection of F. nucleatum while the production of IL-1β was nearly unchanged. Above all, DMOG suppressed F. nucleatum-stimulated IL-6, IL-8, TNF-α, and IL-1β expressions.

Conclusions

These data indicate that prolyl hydroxylase inhibitor DMOG partly downregulates inflammatory cytokine expression in F. nucleatum-infected HGFs.

Clinical relevance

DMOG may provide a novel strategy for the therapy of periodontitis.

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Funding

This research was supported by the National Natural Science Foundation of China (Nos. 81670993 and 81873716), the Key Research and Development Program of Shandong Province (No. 2018GSF118065), the Fundamental Research Funds of Shandong University (No. 2018JC005), the Medical and Health Science and Technology Development Program of Shandong Province (No. 2016WS0339), the National Key Research and Development Program of China (No. 2017YFA0104604), and the Construction Engineering Special Fund of “Taishan Scholars” of Shandong Province (No. ts201511106, No. tsqn20161068).

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Correspondence to Shaohua Ge.

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Ethics approval was gained from the Medical Ethical Committee of School of Stomatology, Shandong University (Protocol Number: GR201603).

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Shang, L., Kang, W., Li, S. et al. Prolyl hydroxylase inhibitor DMOG suppressed inflammatory cytokine production in human gingival fibroblasts stimulated with Fusobacterium nucleatum. Clin Oral Invest 23, 3123–3132 (2019). https://doi.org/10.1007/s00784-018-2733-2

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