Oral lichen-planus-associated fibroblasts acquire myofibroblast characteristics and secrete pro-inflammatory cytokines in response to Porphyromonas gingivalis lipopolysaccharide stimulation

Abstract

BackgroundOral lichen planus (OLP) is a chronic inflammatory oral mucosal disease in which comprehensive inflammation-related cytokines are involved. These cytokines are commonly produced by immune cells and specific nonimmune cells including keratinocytes, endothelial cells and fibroblasts. This raises the question of whether fibroblasts in OLP lesions contribute to the inflammatory process upon inflammatory simulation.MethodsPrimary cultured Oral lichen-planus-associated fibroblasts (OLP AFs, n = 5) and normal buccal mucosal fibroblasts (NFs, n = 5) were examined by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reactions (RT-PCR). Various inflammatory mediators were evaluated with a multiplex assay. Differences among groups were assessed using a Student’s test or repeated measures one-way ANOVA, as appropriate.ResultsOLP AFs express significantly higher levels of α-smooth muscle actin (α-SMA) than NFs, indicating the presence of myofibroblasts. Myofibroblasts secrete Interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) in response to Porphyromonas gingivalis lipopolysaccharide (pg. LPS).ConclusionOLP AFs demonstrated α-SMA expression and secreted pro-inflammatory cytokines in response to pg. LPS stimulation.Electronic supplementary materialThe online version of this article (10.1186/s12903-018-0656-6) contains supplementary material, which is available to authorized users.

N‑acetyl cysteine inhibits the lipopolysaccharide‑induced inflammatory response in bone marrow mesenchymal stem cells by suppressing the TXNIP/NLRP3/IL‑1β signaling pathway

“…A number of studies have demonstrated that LPS-induced overproduction of IL-1β, il-6 and TnF-α contributes to the majority of inflammatory responses that are involved in the pathogenesis of inflammatory-stimulated oral bone diseases, including periodontitis (35), peri-implantitis (36) and apical periodontitis (37). By contrast, our previous studies identified that NAC inhibited LPS-mediated synthesis of IL-1β, il-6 and TnF-α (10,26). Thus the present study focused on the secretion of IL-1β, il-6 and TnF-α.…”

“…The principal etiological factor for these inflammatory diseases is plaque accumulation ( 7 , 8 ). Among the vast array of oral bacteria, Porphyromonas gingivalis serves a particularly important role in both periodontitis and peri-implant diseases, resulting from the expression of various virulence factors, the most recognizable of which is lipopolysaccharide (LPS) ( 9 , 10 ). LPS, also known as endotoxin, induces a variety of cell types, such as osteoblasts ( 11 ), human umbilical vein endothelial cells ( 12 ) and gingival fibroblasts ( 13 ), to overexpress related inflammatory factors, including interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNF-α).…”

“…It is used as a tool for inhibiting the release of inflammatory factors and reducing the inflammation triggered by LPS ( 11 ), as well as in the treatment of different diseases ( 23 – 25 ), including cardiovascular diseases, respiratory diseases and cancer. In our previous studies ( 10 , 11 , 26 ), human umbilical vein endothelial cells, osteoblasts and periodontal ligament fibroblasts were pretreated with NAC prior to their stimulation with LPS. The results demonstrated that this pretreatment led to the inhibition of IL-1β, IL-6 and TNF-α, and the inflammatory response initiated by LPS.…”

Interleukin‑6 released by oral lichen planus myofibroblasts promotes angiogenesis

“…Portal myofibroblasts promote vascular remodeling underlying cirrhosis formation by releasing microparticles (10). A previous study suggested that OLP-associated fibroblasts acquired the characteristics of myofibroblasts (termed OLP/MFs) (11). Immunophenotypically, myofibroblasts are characterized by the expression of abundant pericellular matrix proteins, including vimentin, α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) (11).…”

Oral lichen planus: a microbiologist point of view

“…In 2013 , Ertugrul and colleagues observed that OLP patients were more likely to suffer from infections by Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Prevotella intermedia , Tannerella forsythia , and Treponema denticola , as compared to people not affected by the disease; the conclusion was that all these bacterial species can be involved in periodontal diseases. More recently, Wang et al ( 2018 ) reported that P. gingivalis lipopolysaccharide (LPS) somehow affected fibroblasts in OLP patients, and the cells acquired myofibroblastic characteristics, thus secreting pro-inflammatory cytokines.…”