Gang Zhou

Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form.

BACKGROUNDnNuclear factor-kappa B (NF-kappaB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) in OLP and their expression pattern in relation to several clinical features.nnnMETHODSnThirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-kappaB p65 and TNF-alpha of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls.nnnRESULTSnNuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-alpha staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-kappaB p65 and TNF-alpha were significantly different with respect to clinical forms and lesion sites (P < 0.05), except for genders (P > 0.05) in 30 OLP cases. NF-kappaB nuclear staining positively correlated (r = 0.676, P < 0.01) with TNF-alpha overexpression in OLP.nnnCONCLUSIONSnNuclear factor-kappa B activation and its correlation with overexpression of TNF-alpha may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-kappaB and TNF-alpha, which may contribute to inflammation in OLP; NF-kappaB may also protect epithelial keratinocytes from excessive apoptosis.

Inflammation-related cytokines in oral lichen planus: an overview.

Cytokines are powerful mediators which play a central role in both innate and adapted immune responses. Aberrant productions of cytokines may lead to the onset of immune deficiency, allergy or autoimmunity, which are involved in the mechanisms of various immune-mediated inflammatory diseases. Oral lichen planus (OLP) is a chronic inflammation disease affecting the oral mucosa with unknown aetiology. Previous studies have described the abnormal expression patterns of various inflammation-related cytokines, such as IL-1, 2, 4, 5, 6, 8, 10, 12, 17, 18, TGF-β, IFN-γ and TNF-α, in lesions, saliva, serum and peripheral blood mononuclear cells from patients with OLP, which may reflect the immune dysregulation status and emerge as central players in the immunopathogenesis of OLP. Besides, the gene polymorphisms of several cytokines such as IFN-γ, TNF-α, IL-4, IL-10 have been found to be involved in the susceptibility of OLP. In this review, we gave a brief introduction of the characteristics and biological functions of these inflammation-related cytokines and summarized for the first time the current knowledge on the involvement of inflammation-related cytokines in OLP. Further research on the exact roles of these cytokines will aid the understanding of the pathogenesis and the identification of novel therapeutic approaches of OLP.

Lycopene: features and potential significance in the oral cancer and precancerous lesions

Data from epidemiological studies have indicated that diets rich in fruits and vegetables are likely to benefit many aspects of the prevention of oral malignancy. Lycopene is a red-coloured carotenoid predominantly accumulated in tomatoes as well as other fruits and vegetables. It has been claimed to alleviate chronic diseases such as cancers and cardiovascular disease. Hence, the aim of this review is to summarize the features and its potential significance of lycopene in the development, prevention and treatment of oral premalignant lesions and oral cancer. Studies showed that lycopene might have beneficial effects in the management of some premalignant lesions in the oral cavity including oral submucous fibrosis and oral leukoplakia and may be an adjunct in the prevention and therapy of oral cancer. However, more mechanistic studies and randomized controlled trials of large sample size are necessary to further confirm these effects and to eventually make lycopene to be used in the community prevention and clinically routine management of these diseases.

The efficacy of topical intralesional BCG-PSN injection in the treatment of erosive oral lichen planus: a randomized controlled trial

BACKGROUNDnNowadays, it has been widely accepted that the local cell-mediated immunologic disorders may play an important role in the pathogenesis of oral lichen planus (OLP). Therefore, we sieved out polysaccharide nucleic acid fraction of bacillus Calmette-Guerin (BCG-PSN) from various immunomodulators to evaluate the short-term therapeutic efficacy and clinical safety of intralesional BCG-PSN injection for erosive OLP.nnnMETHODSnA total of 56 OLP patients were randomly assigned to receive either intralesional injection of 0.5 ml BCG-PSN every other day (31 of 56) or 10 mg triamcinolone acetonide (TA, a positive-controlled group, 25 of 56) every week for 2 weeks. After the cessation of treatment, those cured from erosion were followed up for 3 months. Another two researchers measured erosive areas and recorded visual analog scale (VAS) scores both at the start and the end of the treatment. We also registered adverse reactions and the recurrence intervals.nnnRESULTSnAfter 2-week treatment, 27 of 31 BCG-PSN-treated patients (87.1%) and 22 of 25 TA-treated patients (88.0%) healed. There were no statistical differences between the two groups in erosive areas (27.86 +/- 27.97 vs. 25.68 +/- 34.65, P = 0.801) and VAS scores (2.45 +/- 1.64 vs. 2.40 +/- 1.38, P = 0.946). Three of 31 BCG-PSN-treated patients (9.7%) vs. 2 of 25 TA-treated patients (8.0%) experienced the swelling or burning sensation (P = 0.827). A total of 49 of 56 patients were followed up. There were no statistical differences in the recurrence rates (33.3% vs. 45.5%, P = 0.386) and intervals (80.89 +/- 26.83 vs. 73.48 +/- 28.11, P = 0.419).nnnCONCLUSIONSnTopical intralesional BCG-PSN injection is as effective as TA for erosive OLP, which suggests that topical intralesional BCG-PSN injection can be a promising therapeutic alternative for erosive OLP, especially for those insensitive, or even resistant, to glucocorticoids.

Increasing CCL5/CCR5 on CD4+ T cells in peripheral blood of oral lichen planus

Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa, in which T helper 1 (Th1) cells are greatly involved. Chemokine CCL5 is required for T cells infiltration and activation. CCR5, one of its receptors, specifically expressed on Th1 cells among CD4(+) T cells, can be up-regulated by Th1 cytokines like interleukin2 (IL-2) and interferon-gamma (IFN-γ), and down-regulated by Th2 cytokines like IL-4. The present study aimed to determine whether CCL5 and CCR5 had effects on the immune response of OLP. We analyzed the proportion of CCR5(+)CD4(+) T cells in CD4(+) T cells using flow cytometry and the serum levels of CCL5, IL-2, IFN-γ, and IL-4 with ELISA. MicroRNA-125a (miR-125a), a blocker of CCL5, was examined with RT-PCR. The results showed both the serum CCL5 and the percentage of CCR5(+)CD4(+) T cells elevated in OLP patients. Serum IL-2 and IFN-γ increased in OLP patients, but IL-4 decreased. MiR-125a was down-regulated in OLP patients, and there was a negative correlation between miR-125a content and the OLP severity which was measured with a RAE (reticular, atrophic and erosive lesion) scoring system. In conclusion, increasing CCl5/CCR5 might participate in the immune response of OLP. Th1-type cytokines environment presented in OLP probably performed as a magnifier for the CCR5. Moreover, miR-125a might be a candidate biomarker to estimate the severity of OLP.

A randomized double-blind, positive-control trial of topical thalidomide in erosive oral lichen planus.

OBJECTIVEnThe objective of this study was to evaluate the short-term efficacy and safety of topical thalidomide for erosive oral lichen planes (OLP) in a prospective randomized, positive-control, double-blind clinical trial.nnnSTUDY DESIGNnSixty-nine patients with erosive OLP received thalidomide 1% paste (n = 37) or dexamethasone 0.043% paste (n = 32) for 1 week. Patients without erosions after initial 1-week treatment were followed for recurrence, whereas those with ongoing erosions received an additional 3-week treatment. Outcome measures included size of erosive area, visual analog scale (VAS) scores, 3-month recurrence rates, and adverse effects at 1 year.nnnRESULTSnAfter 1-week application, both groups showed significant reductions in erosive areas and VAS scores (P < .001). Complete healing occurred in 18 (54.5%) of 33 thalidomide-treated and 17 (56.7%) of 30 dexamethasone-treated patients. Erosive area size (P = .420) and VAS scores (P = .498) were similar between groups. After 1 month of treatment, 24 patients receiving thalidomide (66.7%) and 22 receiving dexamethasone (73.3%) fully healed. There was no difference between groups in recurrence at the 3-month follow-up. Only 2 patients in each group experienced discomfort with treatment, and no adverse reactions were observed over 1 year of follow-up.nnnCONCLUSIONnTopical thalidomide appears as effective as dexamethasone for erosive OLP.

Efficacy and Safety of Dexamethasone Ointment on Recurrent Aphthous Ulceration

OBJECTIVEnRecurrent aphthous ulceration is the most common oral mucosal lesion and may be associated with many systemic diseases. Topical corticosteroids are used frequently for recurrent aphthous ulceration; however, the number of high-quality clinical experiments available is insufficient, and no reports exist on the blood level of corticosteroids after topical usage in the oral mucosa. The objective was to determine the efficacy and safety of dexamethasone ointment in the treatment of recurrent aphthous ulceration and detect serum dexamethasone concentrations in the patients.nnnMETHODSnA randomized, double-blinded, placebo-controlled, parallel, multicenter clinical trial was conducted in 5 centers to compare the efficacy and safety of dexamethasone ointment with placebo. There were 810 patients with minor recurrent aphthous ulcerations screened for study eligibility, and 240 patients were enrolled at 5 centers from March 1, 2009 to April 30, 2010; 120 were assigned randomly to the treatment group and 120 to a control group. Patients were instructed to apply the given agent to the identified ulcer 3 times a day (after meals) for 5 days. The size, pain level, healing ratio, and average duration of ulcers and the safety of the agents were evaluated. The serum concentration of dexamethasone was detected using a high-performance liquid chromatography/mass spectrometry assay.nnnRESULTSnThe results showed that baseline characteristics were similar (P>.5). At day 6 ± 2 after treatment, there was significant difference in the variation of ulcer size between the treatment group (7.167 ± 6.3415 mm(2)) and the control group (4.346 ± 7.0666 mm(2); P = .000); and in the variation of pain level between the treatment group (5.623 ± 1.9570) and the control group (4.940 ± 2.2449; P = .001). The healing ratio was 83.33% in the treatment group and 54.70% in the control group (P = .000). No severe adverse reactions were observed. No serum dexamethasone was detected before or after the use of the agents (<0.502 ng/mL).nnnCONCLUSIONnDexamethasone ointment was efficient in the treatment of recurrent aphthous ulceration and was safe as evaluated using clinical assessment and serum level detection.

Increased B7-H1 Expression on Peripheral Blood T Cells in Oral Lichen Planus Correlated with Disease Severity

BackgroundOral lichen planus (OLP) is a chronic and T cell-mediated autoimmune disease whose immunopathogenesis may involve antigen-presentation, T cells activation and migration as well as keratinocytes apoptosis. PD-1/B7-H1 pathway may have a unique function in regulating self-reactive T cells associated with inflammatory response and maintaining tolerance in peripheral tissues. In this study, we aimed to explore the contribution of PD-1/B7-H1 pathway to OLP.MethodsWe determined the expression of PD-1 and B7-H1 on peripheral blood T cells from OLP cases and analyzed their association with disease severity assessed by RAE (reticular, atrophic and erosive lesion) scoring system. In addition, interferon-γ, interleukin (IL)-2, IL-4, IL-10 and soluble PD-1 concentrations in serum were measured using ELISA. Then, we explored the regulation of PD-1/B7-H1 pathway on T cells immune response in OLP by blockade of PD-1 or B7-H1.ResultsWe found that PD-1 and B7-H1 were up-regulated on peripheral blood T cells from OLP patients and B7-H1 expression positively correlated with disease severity of OLP. It is suggested that Th1 dominant inflammatory situation might contribute to the high expression of PD-1 and B7-H1 in OLP. Blockade of PD-1/B7-H1 pathway significantly increased the proliferation, and IFN-γ and IL-2 production of T cells.ConclusionsPD-1/B7-H1 pathway may play an important role in negatively modulating T cell-mediated immune response in OLP, and provide the rationale to employ B7-H1 expression on peripheral blood T cells as a marker of severity of OLP and to develop agonists targeting PD-1/B7-H1 pathway as a promising immunotherapeutic strategy for OLP.

Biologics, an alternative therapeutic approach for oral lichen planus.

Oral lichen planus (OLP) is generally accepted as a chronic and T-cell-mediated autoimmune disease, whose immunopathogenesis may involve antigen presentation, T-cell activation and migration as well as, possibly, tumor necrosis factor-alpha (TNF-α)-induced keratinocytes apoptosis. However, present treatment options for OLP are far from being satisfactory. Recent advances in understanding the pathogenesis of OLP, progress in biologics, and the success of biologic therapies in OLP indicate that biologic agents are facing expanding indications in OLP. In this review, we mainly discuss the role of T cells in the pathogenesis of OLP and several biologic therapies that directly and/or indirectly target T cells to treat OLP.

Expression of T-bet and GATA-3 in peripheral blood mononuclear cells of patients with oral lichen planus

OBJECTIVEnOral lichen planus (OLP) is a T-cell-mediated chronic inflammatory oral disease of unknown aetiology. Imbalanced cytokine production by Th1 and Th2 probably contributes to the pathogenesis of OLP. Growing evidence has suggested that two Th1/Th2-specific transcription factors, T-bet and GATA-3, may play a critical role in the development of Th1 and Th2 immunity. The aim of the present study was to investigate the mRNA expressions of T-bet and GATA-3 in the peripheral blood mononuclear cells of OLP subjects, and their expression patterns in relation to several clinical features.nnnDESIGNnExpressions of T-bet and GATA-3 mRNA in peripheral blood mononuclear cells isolated from twenty-eight OLP subjects and sixteen controls were detected by real-time reverse transcription-polymerase chain reaction.nnnRESULTSnWhen OLP subjects were regarded as a whole group, T-bet mRNA level and the ratio of T-bet/GATA-3 mRNA in OLP subjects were significantly higher (P<0.05) than those in controls. When the OLP subjects were divided according to different clinical forms, genders or age groups, T-bet, but not GATA-3, mRNA levels in reticular (P<0.01), female (P<0.05) and elder (age>55, P<0.05) OLP patients were significantly higher than those in control subjects. T-bet/GATA-3 mRNA ratio only in reticular (P<0.05) OLP subjects was significantly higher than that in control subjects.nnnCONCLUSIONSnThe results implicate a predominant role of Th1-type immune response in pathogenesis of OLP. Different gene expressions of T-bet in different clinical features may indicate different immunoregulatory mechanisms of OLP.