Apoptosis in oral lichen planus

Apoptotic cell death may be a contributory cause of basal cell destruction in oral lichen planus (OLP). Therefore. the purpose of this study was to investigate the rate of apoptosis in OLP and the expression of two proteins (FasR and FasL) regulating this process. Biopsies from 18 patients with histologically diagnosed OLP were investigated, with comparison to normal oral mucosa of healthy persons. For visualisation of DNA fragmentation, the TUNEL method was used. In order to characterise the infiltrating cell population (CD3. CD4, CD8) and expression of FasR and FasL, we used an immunohistochemical technique. The results showed that T cells dominated in the subepithelial cell infiltrate. Within the epithelium the apoptotic cells were confined to the basal cell layer, and more apoptotic cells were seen in areas with basal cell degeneration and atrophic epithelium. There was a prominent expression of FasR/FasL in OLP. with a rather uniform distribution throughout the inflammatory cell infiltrate. In the epithelium, the FasR/FasL expression was more abundant in the basal cell area compared to the suprabasal cell layer. In conclusion, apoptosis within the epithelium is significantly increased in situ in OLP compared to normal oral mucosa, and seems to be related to the epithelial thickness.     

细胞凋亡相关蛋白Bcl-2对OLP病损区淋巴细胞聚集的影响

目的:探讨凋亡相关蛋白Bcl-2在口腔扁平苔藓(OLP)病变中的生物学行为及对OLP皮损中浸润淋巴细胞聚集、分布的影响,进一步了解OLP的发病机制。方法:采用免疫组织化学检测法,与正常口腔黏膜对照,观察分析25例OLP皮损中Bcl-2蛋白的表达水平及淋巴细胞聚集、分布。结果:OLP病损区T细胞中Bcl-2过度表达,固有层淋巴细胞异常克隆、聚集,浸润增加。结论:OLP病损区中T细胞高密度聚集可能是Bcl-2诱导的局部淋巴细胞过度增殖后关联反应。     

Survival signalling in keratinocytes of erythematous oral lichen planus

BACKGROUND: Keratinocytes in oral lichen (OL) planus have been shown to be exposed to potentially cell death-inducing factors such as tumour necrosis factor-alpha (TNF-alpha) and FasL, produced by the cells of the inflammatory infiltrate and by the keratinocytes themselves. Mostly, however, the lesions do not show ulceration, the clinical manifestation of substantial keratinocyte death. The aim of this study was to find support for the contention that there is activation of protecting anti-apoptotic mechanisms in keratinocytes in a form of chronic OL (erythematous OL; ERY OL), simultaneously with the pathological cell death signals. METHODS: Biopsies from patients with normal oral mucosa (NOM) or with ERY OL were compared by immunohistological staining. RESULTS: In ERY OL keratinocytes, both the pro-apoptotic FADD and the anti-apoptotic molecules p-IKK, NF-kappaB/p50, FLIP(L), cIAP-1 and cIAP-2 were strongly upregulated when compared with NOM. There were no significant differences in the staining patterns for active caspase-3 and caspase-8 with only few positive cells for both enzymes. CONCLUSIONS: The presently observed marked increase in expression of anti-apoptotic molecules in ERY OL epithelium may counteract the pro-apoptotic assault and rescue the epithelium from rampant cell death and thereby clinical ulceration.     

Induction and upregulation of adhesion receptors in oral and dermal lichen planus

The expression pattern of well-defined cell surface adhesion receptors called VLA-family, LFA-1 and ICAM-1 was determined semiquantitatively in biopsies of oral (n = 12) and dermal lichen planus (n = 5) and compared to normal uninvolved human oral mucosa (n = 12) and skin (n = 12) using an indirect immunoperoxidase technique. In both oral and dermal lichen planus, an induction of the beta 1-integrins VLA-1 and VLA-3 and an upregulation of VLA-6 was found in T cells infiltrating the basement membrane zone. These cell surface molecules function as receptors for collagen, fibronectin and laminin. A focal induction of ICAM-1 on basal keratinocytes could be detected at sites of intramucosal T cells. These results suggest that investigated adhesion receptors are crucially involved in the aggregation of T cells in both conditions. Further investigations have to be done to determine the functional role of these adhesion receptors in lichen planus.     

Psychological profile in oral lichen planus

AIM: Oral lichen planus (OLP) is an oral lesion with an enigmatic etiology. To explore the possibility of psycho-somatization, we evaluated the psychological personality profiles of OLP patients. METHODS: Twenty patients with reticular; 20 with erosive form of OLP, and 25 controls were tested with the psychological Minnesota Multiphasic Personality Inventory (MMPI)-202 test. Eight clinical scales (hypochondriasis, depression, hysteria, psychopathic deviate, paranoia, psychasthenia, schizophrenia, and hypomania) as well as cortisol level, CD3, CD4, CD8, and CD16 markers by group were compared. Psychosomatization was evaluated by the use of internalization ratio (IR) Index. RESULTS: A characteristic MMPI profile was noted in the OLP groups with high IR index value. Significant differences among the groups were detected for cortisol, CD4, CD8, and CD16 counts. Mean values for hypochondriasis, depression, and hysteria were all significantly different with significantly higher mean scores for both reticular and erosive OLP subjects compared with controls. CONCLUSIONS: Prolonged emotive stress in many OLP patients may lead to psychosomatization and may contribute to the initiation and clinical expression of this oral disorder. Clinical significance: If additional research involving a larger and more diverse sample of patients confirms these findings, clinical trials will be needed to determine whether adjunctive psychological intervention provides a benefit in treating patients with OLP.     

Granular cells in oral lichen planus

OBJECTIVE AND DESIGN: Three cases of granular cells associated with oral lichen planus (OLP) have been reported to date, which prompted us to look for the presence of granular cells in a consecutive series of 250 cases of OLP in the period 1996-1998. RESULTS: Only one case with granular cell changes was encountered in that series. H&E stained slides as well as direct immunofluorescence examination showed characteristics compatible with OLP. Part of the subepithelial connective tissue was replaced by a granular cell proliferation; S-100 protein was diffusely expressed in all granular cells, whereas no expression of smooth muscle actin was observed. CONCLUSION: Based on these findings it seems unlikely that the granular cells in the present case represent a so-called 'oral ceroid granuloma'. The presence of granular cells might rather have been a reactive phenomenon triggered by the inflammatory infiltrate or a granular cell tumour (GCT). Whether the simultaneous presence of a GCT and OLP in this particular case was based on a causal relationship or on coincidence still remains unknown.     

Associations between mast cells and laminin in oral lichen planus

Mast cell numbers are increased significantly in oral lichen planus (OLP). In other inflammatory conditions, mast cells frequently adhere to extracellular matrix proteins such as laminin. The aim of this study, therefore, was to determine whether the distribution of mast cells in OLP is related topographically to laminin in vascular and epithelial basement membranes. Monoclonal antibodies for tryptase, laminin and the α6β1 CD49f laminin-binding integrin were used to identify mast cells, basement membranes (blood vessels and basal epithelium) and the "classical" laminin adhesion receptor, respectively. A double-labelling immunoperoxidase technique was employed to examine and compare mast cell-laminin relationships in OLP (n=19) and normal buccal mucosa (NBM, n=13). In both OLP and NBM, the majority of mast cells were located close to vascular basement membranes. Quantitative studies revealed that the number of mast cells associated with the laminin of vascular basement membranes (distance <1 μm) was two-fold and three-fold higher, respectively, in the superficial and deep layers in OLP compared with NBM (P<0.001). The frequency distribution of mast cells associated with basal epithelium was not statistically different in both groups (P>0.05). The association of mast cells with laminin may be an important determinant of mast cell density in OLP. During OLP lesion formation and progression, the preferential distribution of mast cells in the immediate perivascular region provides an ideal situation for mast cell-derived mediators to influence the vascular endothelium.     

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口腔扁平苔藓(orallichenplanus,OLP)是一种累及口腔黏膜且可反复发作的慢性炎症疾病,患病率为0.51%,在口腔黏膜疾病中居第2位,属常见病。皮肤和黏膜可单独或同时发病,病理表现相似:主要以口腔黏膜不同程度的角化异常、基底层细胞液化变性、上皮下结缔组织中淋巴细胞呈带状浸润为典型表现。     

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.     

微小RNA在口腔扁平苔藓中的作用

微小RNA家族在调控基因表达中的重要作用日益受到关注,其调控的基因涉及细胞增殖、凋亡、生长、分化和代谢、血管化和免疫应答等多种生物过程,其表达谱和表达量的变化与多种疾病如肿瘤、炎症性疾病、自身免疫性疾病的发生、发展密切相关.本文对口腔扁平苔藓中微小RNA的研究现状作一综述.     

The frequency of Candida in oral lichen planus

ABSTRACT – Histologic material of typical lichen planus lesions from 43 patients was studied. Two sections of each specimen were stained with hematoxylin-eosin and 10 sections by the PAS method. Only 1 of 43 biopsies was invaded by Candida, and hyphae were present in all of the 10 PAS-stained sections of this case. The results show that oral lichen planus has a considerably lesser susceptibility than oral leukoplakia to invasion by Candida albicans.     

TLR4 and TLR9 are induced in oral lichen planus

J Oral Pathol Med (2012) 41 : 741–747 Background: The role of Toll‐like receptors (TLRs) has been elucidated in many human infectious, autoimmune and neoplastic diseases. Previously, TLR2 and TLR4 expression in oral lichen planus (OLP) was described. The aim of our study was to examine expression patterns of TLR4 and TLR9 in normal oral mucosa and OLP and describe the effect of topical tacrolimus treatment on the expression of TLR4 and TLR9 in OLP. Methods: Toll‐like receptor 4 and TLR9 expression was analysed by immunohistochemistry in five samples of normal oral mucosa and 50 samples of OLP (31 representing clinically white and 19 clinically erythematous/erosive lesions). We evaluated also the effect of topical tacrolimus on TLR4 and TLR9 expression in a patient with OLP. Results: Toll‐like receptor 4 and TLR9 expression was increased in OLP epithelium compared with normal epithelium (P < 0.001); no significant difference between the two clinical types of OLP was observed. TLR9 expression was strongest in the superficial layer of the epithelium (P < 0.001), while the expression of TLR4 was strongest in the basal layer (P < 0.001). Treatment of OLP lesions with topical tacrolimus resulted in clinical improvement but had no effect on TLR expression levels. Conclusions: Toll‐like receptor 4 and TLR9 are induced in OLP; our finding confirms the results of a previous study. TLR4 and TLR9 may play a part in the pathogenesis of OLP. Further studies are needed to dissect the definitive role of TLRs in OLP pathogenesis and progression and to determine the effect of tacrolimus on the function of TLRs.     

Immunohistochemical study of oral keratoses including lichen planus

Biopsies of non-ulcerated oral mucosa from 13 patients with oral lichen planus and 12 patients with leukoplakia were immunohistochemically stained using monoclonal antibodies to pan T, pan B, T helper and T suppressor/cytotoxic cells and the stained lymphocytes enumerated using an image analyser. The results show the preponderance of T cells infiltrating both oral lichen planus and leukoplakia. The T helper: T suppressor/cytotoxic cell ratio was the same (1:2) for both oral lichen planus and leukoplakia. A similar proportion of T suppressor/cytotoxic cells was found infiltrating the epithelium. These data indicate that T cell subset analysis is of no value in distinguishing oral lichen planus from other oral keratoses.     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.     

DNA ploidy in oral lichen planus,determined by image cytometry

J Oral Pathol Med (2010) 39 : 206–211 Background: The objective of this study was to use image cytometry to determine the degree and frequency of DNA ploidy in biopsies of reticular and atrophic‐erosive oral lichen planus and to analyze 14 karyometric measurements of the nuclei of epithelial cells from each specimen. Methods: A total of 40 slides were analyzed, each of them representing one biopsy of one oral lichen planus (OLP) lesion from each one of the 40 patients (cases) studied. Specimens were embedded in paraffin and comprised 20 slides of reticular oral lichen planus (group R) and 20 slides of atrophic‐erosive oral lichen planus (group AE). Results: Group R, the reticular lichen samples, had 18 diploid cases and two aneuploid cases. Group AE, the atrophic‐erosive lichen samples, had 10 diploid cases, one tetraploid case, and nine aneuploid cases. Of the 14 karyometric measurements of the nuclei of OLP epithelial cells analyzed, the group R mean values for mean density and minimum density were significantly greater than the group AE mean values, and mean roundness in group AE was significantly greater than in group R (t‐test: P < 0.05). Conclusions: The most common degree of DNA ploidy in OLP lesions was diploidy. Comparing the two groups (chi‐square test of association P = 0.021) demonstrated that diploidy was associated with the reticular clinical form of OLP, while aneuploidy was associated with the atrophic‐erosive clinical form of oral lichen planus.     

Expression of lymphocyte function-associated antigen 3 in oral lichen planus

OBJECTIVE: The expression pattern of lymphocyte function-associated antigen 3 (LFA-3) in the buccal mucosa of oral lichen planus (OLP) patients was compared to that of healthy controls to investigate the possible role of LFA-3 in cell interactions within OLP lesions.
MATERIALS AND METHODS: Samples of buccal mucosa from 17 clinically healthy individuals and 17 OLP lesions were analysed. Expression of LFA-3, CD2, CD3 and CD 14 was visualized by an immunoperoxidase technique and assessed microscopically.
RESULTS: In healthy buccal mucosa LFA-3 was expressed on keratinocytes, Langerhans cells within the epithelium and on endothelial cells in the lamina propria. In OLP patients a similar pattern of LFA-3 staining was observed. In addition, cytoplasmic LFA-3, without accompanying surface staining, was seen on a subpopul-ation of macrophage-like cells. Substantial amounts of LFA-3 also appeared to be associated with non-cellular components of the extracellular matrix within the inflammatory infiltrate.
CONCLUSIONS: We have obtained evidence for a previously undescribed localization of LFA-3 within macro-phages, and have observed that expression of LFA-3 is apparently elevated within OLP lesions. LFA-3 may play an important role in the pathogenesis of OLP.     

Ets-1在口腔扁平苔藓中的表达研究

目的 :分析Ets 1(E2 6transformation specific)在口腔扁平苔藓 (OLP)的表达及意义。 方法 :采用免疫组化ABC法检测Ets 1蛋白在 2 0例口腔扁平苔藓和 8例正常口腔黏膜组织中的表达。结果 :70 % (14 /2 0 )的口腔扁平苔藓病例中Ets 1呈阳性表达 ,明显高于正常黏膜组织 ,两者比较有显著性差异 (P <0 .0 5 )。阳性表达率在溃疡型OLP与斑块型OLP间亦有显著性差异 (P <0 .0 5 ) ,并与病程相关 (P <0 .0 5 )。结论 :Ets 1在口腔扁平苔藓中过表达并与其发病有关。     

Verruciform xanthoma occurring within oral lichen planus

A verruciform xanthoma occurring within lichen planus on the lateral aspect of the tongue in a 68-year-old Japanese woman is reported. The features suggest that the condition of altered epithelial turnover, as in repeated epithelial desquamation, may cause the verruciform xanthoma.     

Oxpentifylline is not effective for symptomatic oral lichen planus

BACKGROUND: There are no reliably effective therapies for oral lichen planus (OLP). The aim of the present work was to determine the potential efficacy of oxpentifylline in the management of OLP. METHODS: Fifteen patients (six males, median age for the group 52 years, ranging from 33 to 72) with clinically and histopathologically confirmed OLP were treated with oxpentifylline at a dose of 400 mg three times daily. RESULTS: Only 10 patients completed an 8 week course, the other five having to stop therapy because of adverse effects. Only three patients had any relief of their signs and symptoms of OLP. CONCLUSION: The results indicate that oxpentifylline is unlikely to be of benefit for the treatment of OLP.