Proinflammatory cytokine levels in saliva before and after treatment of (erosive) oral lichen planus with dexamethasone

OBJECTIVE: To explore the potential of detecting the level of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1-alpha), IL-6, and IL-8 in whole unstimulated saliva (WUS) in monitoring the therapeutic effects of topical dexamethasone on these salivary cytokines in subjects with erosive oral lichen planus (OLP). STUDY DESIGN: Thirteen definitively diagnosed OLP subjects were enrolled in the study as were 13 age- and sex-matched controls. The OLP subjects were treated with 0.1% dexamethasone oral rinse for 6 weeks. Prior to treatment and at the end of clinical trial, the visual analog scale (VAS) for symptoms was recorded, WUS was collected and these proinflammatory cytokines were analyzed by ELISA. RESULTS: Following the dexamethasone treatment, the levels of TNF-alpha, IL-1-alpha, IL-6, and IL-8 were decreased significantly, and IL-1-alpha and IL-8 were detected at a level without a statistically significant difference from controls. VAS value was decreased significantly and was found to significantly correlate with the decrease in IL-1-alpha and IL-8 levels. CONCLUSIONS: These preliminary results indicate that salivary analysis of NF-kappaB-dependent cytokines may be applied to monitoring the therapeutic response of OLP.     

糖皮质激素对口腔扁平苔藓辅助性T细胞平衡的影响

目的　明确口腔扁平苔藓 (OLP)患者的Th1 /Th2免疫应答模式,探讨糖皮质激素对OLP患者辅助性T细胞平衡的影响。方法　密度梯度离心法分离OLP患者和对照组外周血单个核细胞,分别用植物血凝素(PHA)和地塞米松刺激OLP患者外周血单个核细胞,采用酶联免疫吸附法,检测培养上清液中干扰素γ(IFN γ)和白细胞介素 4(IL 4)的含量;应用半定量逆转录聚合酶链反应技术,检测培养细胞中IFN γ和IL 4mRNA的表达水平。结果　外周血单个核细胞经PHA诱导培养,OLP患者组IFN γ的水平低于健康对照组 (P<0 05),IL 4的水平高于对照组,但差异无统计学意义(P>0 05),IFN γ/IL 4的比值低于对照组 (P<0 05 )。地塞米松可抑制IFN γ和IL 4的水平(P<0 01),且对IFN γ的抑制作用较IL 4更为显著。结论　OLP患者存在Th1 /Th2的平衡失调,为Th2占优势的免疫应答,糖皮质激素对OLP的Th1 /Th2细胞因子均有抑制作用。     

口腔扁平苔藓患者Th1/Th2的表达及临床意义的研究

目的 观察Th1型和Th2型细胞因子在口腔扁平苔藓(OLP)外周血中的表达。方法 密度梯度离心法分离20例充血糜烂型,16例光滑型OLP病例和19例正常对照组人群的外周血单个核细胞,逆转录-聚合酶链反应法检测各组外周血单个核细胞中IFN-gamma mRNA和IL-4 mRNA的表达;ELISA法检测各组血清中IFN-gamma和IL-4的表达。结果 充血糜烂型和光滑型OLP患者中IL-4 mRNA和蛋白的表达均高于正常对照组,差异有统计学意义(P<0.01);而充血糜烂型和光滑型OLP患者中IFN-gamma mRNA和蛋白的表达均低于正常对照组,差异有统计学意义(P<0.01)。但表达结果在充血糜烂型及光滑型OLP患者组间的差异无统计学意义(P>0.05)。结论 Th1/Th2失衡表达与OLP发病机制密切相关,为临床治疗OLP提供新的思路。     

FOXP3+ T regulatory cells in lesions of oral lichen planus correlated with disease activity

Objective:  The aim of this study was to determine the correlation between the number of FOXP3⁺ T cell in lesions and the disease activity of patients with oral lichen planus (OLP).
Materials and Methods:  The expression of FOXP3 was investigated using immunohistochemical staining and real-time RT-PCR in 23 OLP lesions and 12 controls. Changes of FOXP3⁺ Treg in peripheral blood from three patients' pre and post-treatment were assessed using flow cytometry.
Results:  Few FOXP3⁺ cells were detected in controls, but an increased number of FOXP3⁺ cells were observed in lesions ( n  = 20, 40.99 ± 24.68 cells per high-power field – hpf). Furthermore, the frequency of FOXP3⁺ Treg in reticular OLP ( n  = 7, 63.6 ± 23.2 cells per hpf) was significantly higher than that in erythematous/erosive OLP ( n  = 13, 28.8 ± 16.8 cells per hpf, P  = 0.001). In addition, negative correlation was found between the number of FOXP3⁺ Treg and disease activity (correlation oefficient = −0.557, P  = 0.013). The proportion of FOXP3⁺ Treg showed remarkable increase in peripheral blood from patients after treatment (1.39 ± 0.71% vs 4.91 ± 1.59%).
Conclusions:  These data indicated that FOXP3⁺ Treg were involved in the pathogenesis of OLP and correlated with disease's subtype and activity.     

Immune-expression of HSP27 and IL-10 in recurrent aphthous ulceration

Background:  Recently, abnormal cellular immune response has been considered responsible for the oral lesion in the recurrent aphthous ulceration (RAU). For reasons not yet defined, antigens of the oral microbiota would trigger abnormal Th1 immune response against epithelial cells. On the other hand, studies have demonstrated that heat shock proteins (HSP) can block the production of proinflammatory cytokine through inhibition of NF-κB and mitogen-activated protein kinase pathways or activate anti-inflammatory cytokines and therefore control the magnitude of the immune response. HSP27 has been considered a powerful inductor of IL-10, a major inhibitor of Th1 response.
Methods:  Using immunohistochemistry, we studied the expression and location of HSP27 and IL-10 in ulcerated lesions clinically diagnosed as RAU ( n  = 27) and to compare it with that of oral clinically normal mucosa (CT; n  = 6) and of other inflammatory chronic diseases such as oral fibrous inflammatory hyperplasia (FIH; n  = 18), Crohn's disease (CD; n  = 10) and ulcerative colitis (UC; n  = 9).
Results:  A lower proportion of HSP27-positive epithelial cells in RAU and CD were observed when compared with CT and FIH ( P  < 0.001**; P  = 0.013**). A lower proportion of IL-10-positive interstitial cells in RAU was observed when compared with FIH, UC, CT and CD ( P  < 0.001**; P  < 0.001**; P  < 0.001**; P  = 0.034*).
Conclusion:  Altogether the data suggest that a reduced cellular expression of HSP27 and IL-10 in RAU might be related with the aetiopathogenesis of the ulcerated oral lesions.     

Production of proinflammatory and immunoregulatory cytokines by inflammatory cells from periapical lesions in culture

Background:  The role of cytokines in pathogenesis of periapical lesions is not well understood. The aim of this study was to study the correlation between proinflammatory and immunoregulatory cytokines in periapical lesions and their relationship with cellular composition and clinical presentation.
Methods:  Inflammatory cells were isolated from 67 human periapical lesions and cultivated for 24 h. The levels of proinflammatory cytokines: interleukin-1 beta (IL-1β), IL-6, IL-8 and tumour necrosis factor alpha (TNF-α) and immunoregulatory cytokines: transforming growth factor-beta (TGF-β) and IL-10 were determined in culture supernatants using a fluorescent bead immunoassay or ELISA. The phenotype of cells was analysed by immunocytochemistry.
Results:  Inflammatory cells from symptomatic lesions which contained higher proportion of granulocytes, secreted higher levels of IL-1, IL-6 and IL-8 compared with asymptomatic lesions. Large-size lesions contained lower percentages of mononuclear phagocytes, higher percentages of CD8⁺ T cells and produced higher levels of TNF-α, IL-6 and IL-10 compared with small-size lesions. There were negative correlations between the concentrations of TGF-β and proinflammatory cytokines. TGF-β, added to cultures, downregulated the levels of proinflammatory cytokines more strongly than IL-10, independently of clinical presentation of the lesions. By contrast, exogenous IL-10 was mainly immunosuppressive in cultures of asymptomatic lesions.
Conclusion:  Symptomatic lesions are characterized by higher production of proinflammatory cytokines. Immunoregulatory cytokines are more important for suppression of inflammation in asymptomatic lesions and in this context the effect of TGF-β is more potent and different from IL-10.     

The efficacy of topical hyaluronic acid in the management of oral lichen planus

Background:  The aim of this study was to evaluate the efficacy of a topical hyaluronic acid (HA) gel preparation (0.2%) in the management of oral lichen planus (OLP).
Methods:  A total of 124 patients with erosive OLP participated in a randomized, placebo-controlled, double-blind trial to evaluate the efficacy of a topical HA preparation. Outcome measures included soreness relief following immediate application, oral function and size of erosive/ulcerative area. Patients were medicated for 28 days and completed a log diary recording oral function and soreness scores.
Results:  Application of topical HA produced a significant reduction ( P  < 0.05) in soreness scores when compared with placebo for up to 4 h post-application. There was no difference between treatment groups ( P  > 0.05) with respect to oral function. Patients treated with 0.2% HA showed a significant reduction ( P  < 0.05) in the size of the erosive/ulcerated area after 28 days of treatment when compared with baseline. There was no significant difference in changes in ulcerative areas between treatment groups.
Conclusions:  Topical HA (0.2%) does appear to be of some benefit in the management of erosive lichen planus providing efficacy for up to 4 h after administration. Very frequent applications should be considered to obtain a more significant clinical benefit. Topical HA gel may be a useful addition to the treatment option for OLP.     

Distribution of interleukin-2, -4, -10, tumour necrosis factor-alpha and transforming growth factor-beta mRNAs in oral lichen planus.

In the present study, MRNA for the cytokines interleukin-2 (IL-2), IL-4, IL-10 tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor beta-1 (TGF-beta-1) were investigated in oral lichen planus (OLP) lesions using in situ hybridization with 35S-labelled oligonucleotide probes on frozen tissue sections. In addition, the expression of interferon-gamma (IFN-gamma), IL-10 and IL-4 mRNAs was analysed in cultured lesional T lymphocytes from oral lichen planus by polymerase chain reaction. Cells expressing mRNA for IL-2, IL-4, IL-10, TNF-alpha and TGF-beta 1 were found in all the biopsies studied. Approximately 1-2% of the total number of infiltrating cells in the lesions were positive for each of the different cytokine mRNAs. Most biopsies contained basement membrane-oriented, mRNA-positive cells. In the cultured T-cell lines, message for IFN-gamma was detected in all the patients, IL-10 in all but one, and IL-4 in just one of the seven patients investigated. The results suggest that mRNA for both pro- and anti-inflammatory cytokines, i.e., mixed T-helper 1 (TH1) and TH2 cytokine profiles, are generated simultaneously by a limited number of cells in chronic lesions of OLP.     

Salivary interleukin-1β concentration and the presence of multiple pathogens in periodontitis

Aim: This study aimed to find salivary enzymes and/or cytokines that would reflect periodontitis, alone or in combination with salivary microbial markers.
Material and Methods: The salivary concentrations of elastase, lactate dehydrogenase, interleukin-1 β (IL-1 β ), interleukin-6, and tumour necrosis factor- α , and the presence of five periodontal pathogens, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia , and Treponema denticola , were analysed from salivary specimens of 165 subjects, a subpopulation of Health 2000 Health Examination Survey in Finland; 84 of the subjects had probing pocket depth (PPD) of 4 mm at 14 or more teeth (the advanced periodontitis group), while 81 subjects had no teeth with PPD of 4 mm (the control group). All subjects had at least 20 teeth and no systemic diseases.
Results: Among the salivary cytokines and enzymes tested, IL-1 β was the only biomarker associated with periodontitis. An association was also found with the presence of multiple periodontal pathogens. Salivary IL-1 β and the presence of multiple periodontal pathogens were associated with periodontitis at the same magnitude, when they were in the logistic regression model individually or together.
Conclusion: We suggest that salivary IL-1 β and the presence of multiple periodontal pathogens in saliva should be studied more thoroughly as markers of periodontitis.     

Effect of desquamative gingivitis on periodontal status: a pilot study

Objective:  Desquamative gingivitis (DG) represents the gingival manifestation associated with several mucocutaneous disorders and systemic conditions. Little is known of whether or not DG could influence the onset or progression of plaque-related periodontitis. In this study, the potential impact of DG on plaque-related attachment loss and pocket formation has been evaluated.
Methods:  A cross-sectional evaluation of 12 patients with DG [eight oral lichen planus (OLP), four mucous membrane pemphigoid (MMP)], never treated for DG lesions or plaque-related periodontitis, was carried out. Probing depth (PD), clinical attachment loss (CAL), full-mouth plaque (FMPS), and bleeding (FMBS) scores were evaluated at six sites per tooth. Clinical parameters of sites with DG lesions were compared with that of DG unaffected sites.
Results:  Median PD and CAL, as well as FMPS and FMBS, were not significantly different ( P  > 0.05 Mann–Whitney test) for both OLP and MMP patients. However, a negative association between DG lesions and PD < 4 mm (OLP: OR = 0.26; MMP: OR = 0.47), and a positive association with PD 4–6 mm (OLP: OR = 3.76; MMP: OR = 2.68) and with PD > 6 mm (only for OLP: OR = 3.83) were found to be significant.
Conclusions:  The potential interference between DG lesions and periodontitis needs further prospective investigation; nonetheless, a higher level of attention might be prudent.     

The expression and significance of interleukin-35 receptor in oral lichen planus

目的 通过检测白细胞介素35受体（IL-35R）两亚基糖蛋白130（gp130）、白细胞介素12受体β2（IL-12Rβ2）及信号转导和转录激活因子（STAT）1、STAT4在口腔扁平苔藓（OLP）组织中的表达,探讨IL-35R在OLP病损形成和发展中的作用及意义。方法 收集41例OLP组织（OLP组）和15例正常口腔黏膜组织（对照组）为研究对象。采用实时荧光定量聚合酶链反应检测组织中gp130、IL-12Rβ2、STAT1、STAT4 mRNA的表达水平,免疫组织化学（IHC）检测组织中gp130、IL-12Rβ2蛋白的表达及分布,并分析gp130、IL-12Rβ2蛋白表达与OLP临床特征的关系。结果 1）OLP组gp130、IL-12Rβ2、STAT1、STAT4 mRNA的相对表达量均高于对照组（P<0.05）。2）OLP组gp130、IL-12Rβ2蛋白的阳性表达率均高于对照组（P<0.05）,且gp130、IL-12Rβ2蛋白在OLP组织中的表达呈正相关（r=0.984,P<0.001）。3）糜烂型OLP组织gp130、IL-12Rβ2蛋白的阳性表达率高于非糜烂型（P<0.05）。结论 IL-35R及STAT在OLP组织中表达上调,且IL-35R的表达与OLP的临床分型有关,提示IL-35R可能在OLP病损形成及发展中起重要作用。     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Polymorphic drug metabolizing CYP‐enzymes – a pathogenic factor in oral lichen planus?

Background:  Oral lichen planus (OLP) is a chronic mucosal disease with a characteristic clinical phenotype. Environmental exposures, e.g. drugs have been associated with the pathogenesis.
Objectives:  To test the hypothesis that some OLP lesions have a pharmacological pathogenesis related to polymorphisms of the cytochrome P450 enzymes (CYPs) resulting in poor or intermediate CYP metabolism.
Methods:  One hundred and twenty patients with OLP and 180 gender-matched controls without OLP were genotyped for CYP2C9 , CYP2C19 , and CYP2D6 alleles with absent or reduced function.
Results:  The prevalence of poor or intermediate metabolizers was not higher among the OLPs as compared with the controls; however, there were higher numbers of variant CYP2D6 genotypes among the OLP females ( P  < 0.05). There were no differences between the groups with regard to intake of drugs metabolized by polymorphic CYPs or drug or herbal products inhibiting CYPs. The prevalence of CYP2D6*4 alleles among the OLPs was higher [28%; 95% confidence interval (CI) 20–36%] than previously reported among Danes (19%; 95% CI 17–22%). Fifty per cent of the OLPs had a CYP2D6*4 genotype as compared with 30% in the background population ( P  = 0.0001). The CYP2D6*4 protein has sequence homology with human herpes simplex virus type 1 (HSV1) and Candida albicans , which may result in molecular mimicry.
Conclusion:  It was not possible to substantiate a pharmacological pathogenesis of OLP based on poor or intermediate CYP metabolism. However, molecular mimicry between CYP2D6, in particular CYP2D6*4, and common oral pathogens may be involved in the pathogenesis of OLP.     

口腔扁平苔藓患者Th1／Th2失衡表达的研究

目的：观察口腔扁平苔藓（oral liclaen planus,OLP）患者外周血中Th1、Th2型细胞转录因子T-het和GATA-3以及Thl、Th2型细胞因子的表达,进一步探索OLP的发病机制。方法：通过密度梯度离心法分离20例充血糜烂型,16例光滑型OLP病例和19例正常对照组人群的外周血单个核细胞,逆转录-聚合酶链反应（RT—PCR）法检测各组外周血单个核细胞中T—betmRNA和GATA-3 mRNA的表达;ELISA法检测各组血清中干扰素-γ（interferon gamma,IFN-1）和白细胞介素-4（interleukin-4,IL-4）的表达。结果：充血糜烂型和光滑型OLP患者中T—betmRNA、IFN-γ的表达均低于正常对照组,差异有统计学意义（P〈0．01）;而充血糜烂型和光滑型OEP患者中GATA-3 mRNA、IL-4的表达均高于正常对照组,差异有统计学意义（P〈0．01）。T—bet mRNA和GATA-3 mRNA的表达在充血糜烂型及光滑型OLP患者组间的差异有统计学意义（P〈0．01）;而IFN-γ和IL-4的表达在充血糜烂型及光滑型OLP患者组间的差异无统计学意义（P〉0．05）。结论：Th1／Th2失衡表达与OLP发病机制密切相关,为临床治疗OLP提供参考。     

Expression of IFN-γ before and after treatment of oral lichen planus with 0.1% fluocinolone acetonide in orabase

Background:  Oral lichen planus (OLP) is a common chronic inflammatory mucosal disease in which T-cell-mediated immune responses are implicated in the pathogenesis. The purpose of this study was to investigate the effect of 0.1% fluocinolone acetonide in orabase (FAO) on the in situ expression of IFN-γ in patients with OLP.
Methods:  Twenty OLP patients were enrolled in this study. Biopsy specimens and serum samples were obtained before and 1-month after the treatment with 0.1% FAO. In situ expression and serum levels of IFN-γ were determined using immunohistochemistry and ELISA, respectively.
Results:  The number of IFN-γ-positive mononuclear cells in OLP lesions before the treatment was significantly higher as compared with that after the treatment. Similarly, the mean number of total mononuclear cells was clearly decreased after the treatment. However, the serum levels of IFN-γ were not detectable.
Conclusions:  Our results suggest that IFN-γ expression in OLP tissue may involve in the immunopathogenesis and the treatment with 0.1% FAO had an immunomodulating effect on the decrease of IFN-γ.     

Th1 cytokines in oral lichen planus

BACKGROUND: Cell-mediated immune responses in oral lichen planus (OLP) may be regulated by cytokines and their receptors. METHODS: In situ cytokine expression and in vitro cytokine secretion in OLP were determined by immunohistochemistry and ELISA. RESULTS: The majority of subepithelial and intraepithelial mononuclear cells in OLP were CD8+. In some cases, intraepithelial CD8+ cells were adjacent to degenerating keratinocytes. CD4+ cells were observed mainly in the deep lamina propria with occasional CD4+ cells close to basal keratinocytes. Mononuclear cells expressed IFN-gamma in the superficial lamina propria and TNF-alpha adjacent to basal keratinocytes. Basal keratinocytes expressed TNF-alpha as a continuous band. TNF R1 was expressed by mononuclear cells and basal and suprabasal keratinocytes. There was variable expression of TGF-beta1 in the subepithelial infiltrate while all intraepithelial mononuclear cells were TGF-beta1-. Keratinocytes in OLP stained weakly for TGF-beta1. Unstimulated OLP lesional T cells secreted IFN-gamma in vitro. TNF-alpha stimulation down-regulated IFN-gamma secretion and up-regulated TNF-alpha secretion. IL-4, IL-10 and TGF-beta1 secretion were not detected. CONCLUSIONS: These data suggest the development of a T helper 1 immune response that may promote CD8+ cytotoxic T-cell activity in OLP.     

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background:  Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine.
Methods:  This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11–17 years for OSCC (mean 13.3), 12–22 years for OLP (mean 15.9) and 12–17 years for hyperkeratosis (mean 14.5).
Results:  Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 ( n  = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53- mutated out of 31 tested. One TP53- mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site.
Conclusion:  TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.     

A role for the substance P/NK-1 receptor complex in cell proliferation and apoptosis in oral lichen planus

Objectives:  To determine whether substance P (SP) and NK-1 receptor (NK-1R) are expressed in oral lichen planus (OLP) and are related to cell proliferation and apoptosis in this disease.
Material and methods:  Tissue samples from 50 OLP patients and 26 healthy controls were studied. Immunohistochemistry was performed with anti-SP, anti-NK-1R, anti-ki-67 and anti-caspase-3 monoclonal antibodies and the clinical and pathological data of the OLP patients were evaluated.
Results:  With the exception of NK-1R expression in epithelial cell membrane and cytoplasm, all markers were more frequently present in OLP patients than in controls ( P  < 0.05). Higher cytoplasmatic expression of NK-1R was associated with higher epithelial expression of caspase-3 ( P  < 0.05). Higher epithelial expression of NK-1R and SP was associated with higher suprabasal and basal epithelial expression of ki-67 ( P  < 0.05 and P  < 0.005, respectively).
Conclusions:  Actions of the SP/NK-1R complex may contribute to the immune disorder underlying OLP and trigger stimuli to induce cell proliferation. These results indicate that this complex might play a role in the malignant transformation of OLP.     

Cytokine production by keratinocytes and mononuclear infiltrates in oral lichen planus

Cytokine generation by tissue-infiltrating mononuclear cells (TIMC) and by keratinocytes (KC) was investigated in material obtained from the oral mucosal tissues of patients with oral lichen planus (OLP). Peripheral blood mononuclear cells (PBMC) and chronically inflamed and noninflamed gingival KC (CIG-KC, NOR-KC, respectively) were used as the controls. Compared to NOR-KC and CIG-KC, KC from OLP patients (OLP-KC) produced much more interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The OLP-KC superiority in the production of these cytokines was more prominent when the KC were cultured in the presence of interleukin-l beta (IL-1β), lipopolysaccharide and phorbol myristate acetate. OLP-KC also produced more monocyte-chemotactic factor(s) which were not inactivated by the antibodies against GM-CSF, macrophage colony-stimulating factor and monocyte chemoattractant protein-1. TIMC in OLP tissues (OLP-TIMC) were superior to PBMC in the generation of IL-6 and GM-CSF. OLP-TIMC were stimulated to produce more TNF-a by IL-1β, IL-6 and GM-CSF, more IL-6 by IL-1β and GM-CSF, and more GM-CSF by IL-1β and IL-6 than PBMC. When compared to cytokine generation in TIMC from the chronically inflamed gingivae, more interferon-gamma, IL-6 and TNF-α were generated by OLP-TIMC. These results indicate that KC play a critical role in OLP, producing cytokines including monocyte-chemotactic factor(s), and that the cytokines produced by TIMC and OLP-KC through autocrine and paracrine processes enhance the local inflammatory response.