Oral Lichen Planus Mucosa Research Articles

НЕКОТОРЫЕ ОСОБЕННОСТИ СТОМАТОЛОГИЧЕСКОГО СТАТУСА ПАЦИЕНТОВ С ПРОЯВЛЕНИЯМИ ТИПИЧНОЙ И ЭРОЗИВНО-ЯЗВЕННОЙ ФОРМЫ КРАСНОГО ПЛОСКОГО ЛИШАЯ СЛИЗИСТОЙ ОБОЛОЧКИ РТА

The purpose of the study is to evaluation of peculiarities of complaints, symptoms and clinical manifestations of typical asymptomatic (L43.80) and erosive-ulcerative (L43.82) forms of lichen planus (LP), its manifestations on the oral mucosa, depending on the age and sex of patients.
 Material and methods. In the present study, 111 patients with OLP were divided into a main clinical group with erosive-ulcerative form of OLP (L43.82, n = 86) and a comparison group with typical asymptomatic form of OLP (L43.80, n = 25) based on the complex of dental examination and simple randomization method. Mann–Whitney and chi-square tests, including Yates' correction, were used to assess the statistical significance of differences between the groups. 
 Results. Patients with the typical asymptomatic form of OLP (L43.80) often had grayish-white, flat papules up to 2 mm in diameter on the unchanged mucosa of the cheeks and dorsal surface of the tongue in the absence of complaints. In the erosive and ulcerative form (L43.82) of OLP, the complaints of pain, intensifying at intake of hard, spicy and hot food, feeling of tightness, roughness, burning, slight dryness prevailed, papules, erosions of irregular or polygonal ulcers were simultaneously observed on swollen, hyperemic mucosa of cheeks, corners of mouth and lateral surface of tongue. The studied pathology prevailed in 81.98% of cases in persons of young working age. Depending on the form of OLP, the intensity of caries according to the CPU index corresponds to a high or very high degree of caries process, the state of oral hygiene according to the OHI-S index of poor or poor hygiene, the inflammatory process in periodontal tissues according to the PMA index of mild or medium degree of inflammation (p < 0.001). Conclusion: thus, the identified features of complaints, symptoms and manifestations of oral mucosal lichen planus should be taken into account by general practitioners when conducting outpatient appointments.

Infiltration of Mature KLRG1 Expressing Cytotoxic T Cells in Oral Lichen Planus.

Oral lichen planus (OLP) is a chronic inflammatory disease affecting oral mucosa. Its pathogenesis includes T cell infiltration. T cells may be naïve or in response to antigen stimulation, progress through differentiation stages. The differentiated states of T cells in OLP mucosa have not previously been reported. Available OLP microarray gene expression data from Gene Expression Omnibus were analyzed for markers of T cell cytotoxicity. Immunohistochemical studies of T cell subset markers CD4 and CD8 and the T cell differentiation marker killer cell lectin-like receptor G1 (KLRG1) were performed on paraffin embedded formalin fixed oral mucosa biopsy samples from 10 patients with OLP. Gene expression analysis of OLP oral mucosa samples disclosed increased transcript expression of KLRG1, CD8A, and granzyme K (GZMK). By immunohistochemistry, prominent CD4 + and CD8 + T cell infiltration was seen in all patient samples. KLRG1 + T cells were abundant, constituting a mean of 51% (range 40-65%) of the number of CD8 + T cells. KLRG1 + T cells localized at the epithelium and lamina propria junction, infiltrating both basal and intraepithelial regions and adjacent to both basal and intraepithelial keratinocytes. OLP oral mucosa T cell infiltration includes KLRG1 + highly differentiated cytotoxic T cells, suggesting continued antigen exposure driving T cells to a highly differentiated phenotype. The known phenotype of these cells, together with microarray detected increases in cytotoxic molecules, suggests that highly differentiated cytotoxic T cells contribute to oral mucosa injury in OLP.

Evaluation of clinical efficacy of antiviral treatment of patients with lichen planus of oral mucosa

In the treatment of patients with lichen planus of the oral mucosa and identified papillomovirus infection, the appointment of an immunomodulatory drug with antiviral activity is of particular importance.Aim. To evaluate the clinical efficacy of antiviral and immunomodulatory drug inosine pranobex in the treatment of lichen planus of oral mucosa.Materials and methods. 49 patients with erosive-ulcerative form (37 women (75.5 %) and 12 men (24.4 %) aged 43 to 68 years, mean age 57.43 ± 2.53 years were under observation. The disease duration ranged from 6 months to 9 (5.58 ± 1.26) years.Results. Inosine pranobex, used in group Ib, showed high efficiency in the treatment of patients: the number of patients with high viral load decreased to zero, and the percentage of patients with clinically significant HPV decreased by half. Eradication of papillomavirus was recorded as a result of antiviral therapy in 11 (73.33 %) patients, while in group Ia such results were not achieved.Summary. According to the results of this study, it was found that for patients with lichen planus of oral mucosa with detected PVI, the appointment of an antiviral drug is necessary. This treatment is characterized by high efficiency and allows to increase the rate of epithelialization of pathological elements by almost 25 %, to achieve clinical remission and to stop the pain symptom faster, thereby improving the quality of life of patients.

Role of the high mobility group box 1 signalling axes via the receptor for advanced glycation end-products and toll-like receptor-4 in the immunopathology of oral lichen planus: a potential drug target?

High mobility group box 1 (HMGB1) is an extremely conserved DNA-binding protein that stabilizes nucleosomes and facilitates gene transcription in mammalian cells. When released extracellularly, HMGB1 becomes an alarmin that can mediate systemic diseases. High mobility group box 1 signals via two main receptors: receptor for advanced glycation end-products (RAGE) and toll-like receptor-4 (TLR4). We hypothesized that HMGB1 expression is increased in patients with oral lichen planus (OLP) relative to healthy controls. Therefore, HMGB1 and its receptors were mapped in tissue biopsies from 25 patients with OLP and from 20 healthy controls by immunostaining and ImageJ analysis. High mobility group box 1 was induced in oral keratinocytes in all patients with OLP. The band-like cell infiltrate in patients with OLP revealed very strong staining for RAGE. Likewise, TLR4 was overexpressed throughout OLP mucosa which co-localized with HMGB1. In conclusion, we suggest that OLP could partly be an HMGB1-mediated condition by creating a proinflammatory loop cycle via RAGE- and TLR4-signalling axes, which may contribute to the chronicity of this disease.

Gene expression of miRNA-138 and cyclin D1 in oral lichen planus.

This study aimed to evaluate microRNA-138 (miR-138) gene expression and its target cyclin D1 (CCND1) gene and protein expression in oral lichen planus (OLP) mucosa in an attempt to investigate their possible roles in OLP immunopathogenesis. Sixty oral biopsy specimens were harvested from 30 healthy subjects and 30 OLP patients, subdivided into reticular, atrophic, and erosive groups (n=10 each). Samples were subjected to quantitative real-time polymerase chain reaction analysis for quantification of miR-138 and CCND1 relative gene expression and immunohistochemical analysis to determine CCND1 protein expression. Samples from OLP patients had a significant underexpression of miR-138 gene and overexpression of CCND1 at both gene and protein levels compared to normal mucosa samples. The lowest levels of miR-138 expression were observed in atrophic and erosive OLP compared to reticular OLP, and the highest levels of CCND1 gene and protein expression were in atrophic OLP. An inverse correlation was demonstrated between the miR-138 expression and both CCND1 gene and protein expression in OLP patients. A significant positive correlation between CCND1 gene and protein expression was also observed. Downregulation of miR-138 increases the gene and protein expression of its potential target CCND1 in OLP mucosa which might have a pivotal role in the disease pathogenesis. This research implied that miR-138 may have a role in identification of symptomatic OLP lesions. MiR-138 might be considered as a potential tool in future OLP molecular therapy.

GENE EXPRESSION OF MIRNA-138 AND CYCLIN D1 IN ORAL LICHEN PLANUS

Objectives: To evaluate microRNA-138 (miR-138) gene expression and its target cyclin D1 (CCND1) gene and protein expression in oral lichen planus (OLP) mucosa in an attempt to investigate their possible roles in OLP immunopathogenesis. Methods: Sixty oral biopsy specimens were harvested from 30 healthy subjects and 30 OLP patients; subdivided into reticular, atrophic and erosive groups (n=10 each). Samples were subjected to quantitative real-time polymerase chain reaction analysis for quantification of miR-138 and CCND1 relative gene expression and immuohistochemical analysis to determine CCND1 protein expression. Results: Samples from OLP patients had a significant underexpression of miR-138 gene and overexpression of CCND1 at both gene and protein levels compared to normal mucosa samples. The lowest levels of miR-138 expression were observed in atrophic and erosive OLP compared to reticular OLP and the highest levels of CCND1 gene and protein expression was in atrophic OLP. An inverse correlation was demonstrated between the miR-138 expression and both CCND1 gene and protein expression in OLP patients. A significant positive correlation between CCND1 gene and protein expression was also observed. Conclusion: Down regulation of miR-138 increases the gene and protein expression of its potential target CCND1 in OLP mucosa which might have a pivotal role in the disease pathogenesis. Clinical relevance: This research implied that miR-138 may have a role in identification of symptomatic OLP lesions. MiR-138 might be considered as a potential tool in future OLP molecular therapy.

MiR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3K/Akt/mTOR pathway.

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that involves the degeneration of keratinocytes. However, the etiology and mechanisms of OLP pathogenesis have not been fully elucidated. In this study, we used keratinocytes HaCaT stimulated with lipopolysaccharide (LPS) to mimic a local OLP immune environment, and investigated the regulatory role of miR-125b in keratinocyte proliferation and apoptosis under OLP conditions. Immunohistochemical analysis and quantitative real-time PCR (qRT-PCR) assay showed that MMP-2 expression was up-regulated and miR-125b expression was down-regulated in both OLP mucosa tissues and LPS-incubated HaCaT cells. Western blot analysis indicated that miR-125b overexpression suppressed LPS-induced MMP-2 expression in HaCaT cells. Molecularly, our results confirmed that MMP-2 is a target gene of miR-125b in HaCaT cells. The effect of miR-125b on cell proliferation was revealed by CCK-8 assay, BrdU assay and cell cycle analysis, which illustrated that miR-125b overexpression impeded LPS-induced HaCaT cell proliferation. Flow cytometry analysis further demonstrated that miR-125b overexpression promoted HaCaT cell apoptosis. Moreover, these effects were involved in PI3K/Akt/mTOR activation, as miR-125b overexpression inhibited LPS-enhanced expression of p-Akt and p-mTOR proteins. Taken together, these data confirm that miR-125b might inhibit keratinocyte proliferation and promote keratinocyte apoptosis in OLP pathogenesis by targeting MMP-2 through PI3K/Akt/mTOR pathway.

Serum TNF-Alpha, IL-12, IL-8 in Patients with Oral Mucosal Lichen Planus

Serum TNF-Alpha, IL-12, IL-8 in Patients with Oral Mucosal Lichen Planus

Oral mucosal lichen planus in childhood

Lichen planus is a relatively common mucocutaneous disorder in adults, but it is rarely reported in children. Much less data is available regarding lichen planus in children. This is a report with intraoral lesions of lichen planus. Lichen planus, although reportedly rare in childhood, should be considered in the diagnosis of hyperkeratotic or erosive lesions of oral mucosa in children.

Efficacy and safety of oral alitretinoin in oral mucosal lichen planus—results of a prospective trial

Efficacy and safety of oral alitretinoin in oral mucosal lichen planus—results of a prospective trial

Novel Cytokines in the Pathogenesis of Oral Mucosal Lichen Planus

Novel Cytokines in the Pathogenesis of Oral Mucosal Lichen Planus

Th17 Immune Cell Expression in Oral Mucosal Lichen Planus (OMLP)

To determine whether Th17 immune cell expression is associated with the clinical type and pathogenesis of oral mucosal lichen planus (OMLP).

Assessment of TNF-á, IFN-ã and IL-4 Levels in Patients with Oral Mucosal Lichen Planus

Assessment of TNF-á, IFN-ã and IL-4 Levels in Patients with Oral Mucosal Lichen Planus

Oral mucosal lichen planus in childhood

Lichen planus is a relatively common mucocutaneous disorder in adults it's rarely reported in children. However, much less data are available regarding lichen planus in children. Here is a report with intraoral lesions of lichen planus. Lichen planus, although reportedly rare in childhood, should be considered in the diagnosis of hyperkeratotic or erosive lesions of the oral mucosa in children.

In vitro culture system for keratinocytes obtained from oral lichen planus lesions

The aim of this study was to establish a stable in vitro culture system for keratinocytes obtained from oral lichen planus (OLP) lesions and evaluate cultured keratinocyte characteristics including cell morphology, ultrastructure, and expression of biomarkers. OLP mucosa (histopathologically confirmed) was collected and cells isolated using the cold enzyme digestion method. Primary culture and serial passage were performed on serum-free keratinocyte medium. Morphological changes of cells were evaluated via inverted phase contrast microscopy, and cellular ultrastructure was observed by electron microscopy. Indirect immunofluorescence was used to detect expression of keratin and nuclear factor-kappaB (NF-κB). OLP type I keratinocytes was successfully cultured in vitro in serum-free medium. Cellular morphology was typically polygonal during the growth phase. Cells could be passaged continuously for five to six generations without losing viability. Transmission electron microscopy showed large nuclei and multiple vacuoles in the cultured cells consistent with histopathological features of OLP keratinocytes. Indirect immunofluorescence staining was positive for keratin and NF-κB. This study established that human OLP kera-tinocytes can be successfully cultured cells with histopathologic features and biomarker expression consistent with OLP type I keratinocytes. This culture system lays a foundation for the establishment of human OLP cell model in vitro.

OP058: Development of an algorithm for oral squamous cell carcinoma risk assessment using micro-RNA markers

Purpose The aim was to develop an algorithm for assessment of oral squamous cell carcinoma (OSCC) risk using microRNA (miR) abundance data. Material and methods Quantitative reverse transcription PCR (qRT–PCR) was conducted on RNA isolated from 20 each of formalin fixed and paraffin embedded (FFPE) biopsy samples that were histologically assessed as OSCC or histologically normal epithelium (HNE), as well as additonal oral tissue samples. A panel of 11 miR considered as potential biomarkers of OSCC were assessed with obtained Cq values normalized and statistically analyzed using qBase PLUS (Biogazelle) software. Results Seven miR showed statistically significant abundance differences between the 20 OSCC and 20 HNE. We then developed an algorithm for assessment of OSCC-risk (the “miR-OSCC-risk”) that gave sensitivity and specificity calculations for the HNE and OSCC samples tested. The algorithm output indicated high (flagged as red), indeterminate (amber) or low (green) risk, that showed a sensitivity of 87.5%; specificity of 92.3%; positive predictive value of 93.3%; negative predictive value of 85.7%; and an accuracy of 89.6%. The abundances of the panel miR and the predictive accuracy of the algorithm was tested further using other oral lesion samples. Oral mucosal lichen planus, mild dysplastic lesions and cytological scrapings of normal epithelia were in the majority of instances determined to be of low risk by the algorithm whereas the severely dysplastic lesions were in the majority determined to be of high risk and warranting further clinical and histological investigation. Conclusions The developed miR-OSCC-risk algorithm can be used with qRT-PCR miRNA abundance data to provide an indication of OSCC risk that has potentially significant clinical utility. The diagnostic procedure developed here could be of benefit in the assessment of oral lesions of unknown pathology by the targeting of lesions requiring biopsy.

Does the toll-like receptor 2 (TLR2) play a role in oral mucosal lichen planus (OMLP)?

<h3>Aims</h3> To correlate TLR2 expression with the immunological microcellular environment of oral mucosal lichen planus (OMLP), immune cell surface identification markers (CD3, CD4, CD8, CD19 and CD83) were also studied. <h3>Methodology</h3> 50 FFPE tissue specimens [control group (<i>n</i>=10) and OMLP group (<i>n</i>=40)] were examined for TLR2, CD3, CD4, CD8 CD19 and CD83 expression by immunohistochemistry. In addition, the expression level of 84 human TLR signalling pathway genes in both groups [control group (<i>n</i>=6) and OMLP group (<i>n</i>=6)] was determined in parallel. <h3>Results</h3> CD3⁺, CD4⁺, CD8⁺, CD19⁺and CD83⁺ showed a significantly higher expression of positive cells in OMLP than in the control group (<i>p</i> < 0.05). No TLR2 immunostaining was observed in either group. Twenty TLR signalling pathway genes were expressed significantly in the OMLP group compared to the control group (<i>p</i> < 0.05). Genes that were up-regulated included CXCL10, LTA and IFNG; those down-regulated included HSPD1 and TLR2. <h3>Discussion</h3> Negative TLR2 immunostaining and down-regulation of the TLR2 genes suggests that there was a deactivation of TLR2 receptor. This indicates that OMLP is not associated with host response to pathogens or heat shock protein <i>via</i> TLR2 stimulation of the NF-kβ or JNK/p38 pathways. CD3, CD4 and CD8 positive T cells were the predominant inflammatory cell type in OMLP. High levels of CXCL10, IFNG and LTA cytokines are known to be associated with T cell migration into the developing lesion suggesting that these cytokines play an important role determining the immunological microcellular environment in OMLP.

Does the toll-like receptor 2 (TLR2) play a role in oral mucosal lichen planus (OMLP)?

<h3>Aims</h3> To correlate TLR2 expression with the immunological microcellular environment of oral mucosal lichen planus (OMLP), immune cell surface identification markers (CD3, CD4, CD8, CD19 and CD83) were also studied. <h3>Methodology</h3> 50 FFPE tissue specimens [control group (<i>n</i>=10) and OMLP group (<i>n</i>=40)] were examined for TLR2, CD3, CD4, CD8 CD19 and CD83 expression by immunohistochemistry. In addition, the expression level of 84 human TLR signalling pathway genes in both groups [control group (<i>n</i>=6) and OMLP group (<i>n</i>=6)] was determined in parallel. <h3>Results</h3> CD3⁺, CD4⁺, CD8⁺, CD19⁺and CD83⁺ showed a significantly higher expression of positive cells in OMLP than in the control group (<i>p</i> < 0.05). No TLR2 immunostaining was observed in either group. Twenty TLR signalling pathway genes were expressed significantly in the OMLP group compared to the control group (<i>p</i> < 0.05). Genes that were up-regulated included CXCL10, LTA and IFNG; those down-regulated included HSPD1 and TLR2. <h3>Discussion</h3> Negative TLR2 immunostaining and down-regulation of the TLR2 genes suggests that there was a deactivation of TLR2 receptor. This indicates that OMLP is not associated with host response to pathogens or heat shock protein <i>via</i> TLR2 stimulation of the NF-kβ or JNK/p38 pathways. CD3, CD4 and CD8 positive T cells were the predominant inflammatory cell type in OMLP. High levels of CXCL10, IFNG and LTA cytokines are known to be associated with T cell migration into the developing lesion suggesting that these cytokines play an important role determining the immunological microcellular environment in OMLP.

Oral mucosal lichen planus in children – Report of three cases

Oral mucosal lichen planus in children – Report of three cases

Oral mucosal lichen planus in children – Report of three cases

Oral mucosal lichen planus in children – Report of three cases