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.     

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.     

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.     

Expression of MHC Class II antigens (HLA DR, DP and DQ) by keratinocytes in oral lichen planus

The incidence and distribution of keratinocytes expressing the major histocompatability complex antigens HLA DR, DP and DQ and their relationship to the density of the inflammatory infiltrate was determined in lesions of oral lichen planus and normal mucosa using an immunoalkaline phosphatase technique. Seven of eight biopsies of lichen planus showed evidence of keratinocyte HLA DR expression but the pattern was variable both within and between biopsies. A significant increase in density of lymphocytes was found beneath those areas showing HLA DR expression throughout the prickle cell layer compared with those areas showing patchy or no expression. No evidence for keratinocyte expression of HLA DP or DQ was found. These results suggest that expression of HLA DR by keratinocytes in lichen planus may be induced by the lymphocytic infiltrate perhaps as a result of interferon gamma production. The functional significance of such MHC Class II expression remains unknown.     

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。     

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.     

EP—CAM在OLP和OSCC组织中的表达及意义

目的：观察上皮细胞黏附分子（Ep—CAM）在口腔正常黏膜、扁平苔癣（OLP）和鳞癌（OSCC）组织中表达的变化,分析Ep—CAM在口腔黏膜疾病及其癌变发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、30例OLP（15例非糜烂型、15例糜烂型）及20例OSCC组织中Ep—CAM的表达变化。结果：Ep—CAM在正常黏膜组织阴性表达,而在非糜烂型OLP、糜烂型OLP及OSCC组织中表达逐渐增强。结论：Ep—CAM在口腔黏膜癌变的发展过程中可能具有一定的指示意义。     

口腔扁平苔藓凋亡相关基因的表达及意义

目的：探讨凋亡相关基因P53，Bcl-2,Fas,Fas-L的表达在口腔扁平苔藓（Oral Lichen Planus OLP)病变形成及发展中的作用。方法：采用免疫组化SABC法对28例OLP病损中凋亡调节蛋白P53，Bcl-2,Fas,Fas-L进行检测，并与正常口腔粘膜比较，结果：（1）P53蛋白在正常口腔粘膜中表达阴性，但可在OLP上皮基底细胞及部分棘细胞中表达。（2）Bcl-2蛋白在正常口腔粘膜及OLP病损上皮中表达很弱或阴性，但在OLP固有层浸润的淋巴细胞呈强阳性表达。（3）Fas和Fas-L在正常口腔粘膜及OLP病损上皮中表达差异不显著（P＞0．05），结论：口腔扁平苔藓病变的形成及发展部分归因于凋亡，P53和Bcl-2蛋白对OLP局部上皮病变及炎性细胞浸润的存在可能有一定作用。而Fas和Fas-L系统在OLP病变形成及发展中可能不起主要作用。     

High proliferative activity and chromosomal instability in oral lichen planus

The study aimed to assess the proliferative activity and karyotype in Oral Lichen Planus (OLP) lesions. G-banding chromosomal analysis of short-term primary cultures, and immunohistochemical expression of Ki67 and p53 were applied in 30 consecutive OLP patients divided into two groups according to clinical presentation of the lesions, and in nine subjects as negative controls. Mean values of Ki67 and p53 expression differed significantly (P<.01) between controls and patients groups with reticular or atrophic-erosive forms of OLP, whereas there was no significant difference between the two groups of patients with reticular or atrophic-erosive lesions. Six OLP patients showed clonal chromosome alterations, four of them associated with p53 overexpression. In conclusion, OLP is characterized by a high cellular turnover in most patients irrespective of clinical disease presentation. The genetic instability found in some patients should be interpreted as a consequence of the enhanced epithelial turnover, although we cannot rule out the possibility that some of the cytogenetic non-random anomalies observed represent early steps in cancer development.     

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。     

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.     

辅助性T淋巴细胞极化相关细胞因子在口腔扁平苔藓中的研究进展

口腔扁平苔藓是一种病因不明的皮肤黏膜慢性免疫炎症性疾病,辅助性T淋巴细胞(Thcell)在口腔扁平苔藓的发病机制中起到了重要作用。近年来,口腔扁平苔藓中Th细胞的极化状态引起了较为广泛的关注。研究表明,Th细胞极化相关细胞因子的变化与口腔扁平苔藓的发病密切相关。下文就这些细胞因子在口腔扁平苔藓中的研究进展作一综述。     

口腔黏膜扁平苔藓患者口腔黏膜组织中cyclin D1,ki-67及凋亡的表达研究

目的　检测口腔黏膜扁平苔藓 (OLP)患者口腔黏膜上皮凋亡增殖状况及细胞周期调控蛋白表达水平的变化 ,探讨OLP发病机制。方法　采用甲基绿 -派诺宁法及免疫组化SABC法分别检测 30例OLP患者及 2 0例正常对照者口腔黏膜组织的凋亡情况及细胞周期蛋白 (cyclinD1)、增殖细胞核抗原 (ki 6 7)的表达并进行细胞计数及统计学分析。结果　OLP组与对照组凋亡、ki 6 7、cyclinD1表达阳性率差异有显著性 (P <0 .0 5 ) ;与凋亡呈正相关。结论　OLP病变中 ,部分细胞受损进入凋亡性细胞死亡 ,同时发生了细胞周期紊乱、细胞增殖     

不同临床类型OLP中STAT3的表达及意义

目的：研究不同临床类型的口腔扁平苔藓（OLP）中细胞信号传导和转录激活因子3（STAT3）的表达及意义。方法：采用免疫组织化学方法分别检测10例正常口腔黏膜组织,29例非糜烂型OLP、16例充血糜烂型OLP损害中STAT3的表达。结果：STAT3阳性表达分布于细胞质和细胞核内。正常口腔黏膜、非糜烂型OLP、糜烂型OLP上皮层中STAT3阳性表达率分别为30．00％（3/10）、75．86％（22/29）、93．75％（15/16）;固有层中分别为0％（0/10）、65．52％（19/29）、100．00％（16/16）;三种类型上皮层两两之间相比,差异有统计学意义（P＜0．05）;固有层两两之间相比,只有非糜烂型OLP和糜烂型OLP之间差异没有统计学意义（P＞0．05）。结论：STAT3与OLP上皮层的炎症进程密切相关,对STAT3表达的研究将有助于进一步探究OLP的发病机制和早期临床诊疗。     

KLF-6在口腔扁平苔藓恶变中的表达研究

目的 探讨KLF 6在口腔扁平苔藓发病机制及癌变中的作用。方法 分别采用免疫组化和Western blot方法对10例正常口腔黏膜、30例扁平苔藓患者和22例口腔鳞癌患者的上皮组织中KLF 6蛋白进行t检测,比较其在三者之间的差异。SPSS 14.0对数据进行检验。结果 扁平苔藓患者组织中KLF 6蛋白的表达明显低于正常口腔黏膜,两组之间具有显著性差异;口腔鳞癌患者组织中KLF 6蛋白的表达明显低于扁平苔藓组织,两组之间具有显著性差异。结论 KLF 6的表达异常可能在口腔扁平苔藓的发生发展及癌变的过程中起作用。     

Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection,oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus

OBJECTIVES: Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS: Three groups of OLP patients, (I) OLP-HCV patients (n = 17), (2) OLCSR patients (n = 10) and (3) iOLP patients (n = 14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin-biotin-complex technique. RESULTS: The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION: The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups.     

表皮生长因子受体在口腔扁平苔藓组织中的表达

目的探讨口腔扁平苔藓(OLP)癌变及发病机制。方法采用免疫组化法检测10例正常口腔黏膜,16例扁平苔藓,10例扁平苔藓伴不典型增生,14例口腔鳞癌上皮组织中表皮生长因子受体(EGFR)的表达水平。结果OLP伴不典型增生组织中EGFR的表达高于正常黏膜(P<0.05)。口腔鳞癌中EGFR的表达高于正常黏膜及OLP(P<0.01)。结论EGFR的过表达在OLP的发生、发展过程中可能起着重要的作用。