Objective: To explore the expression of autophagy related factors microtubule associated protein 1 light chain 3B (LC3B), p62, autophagy key factor Beclin1 in oral lichen planus (OLP) tissues and their relationships with the clinicopathological characteristics of OLP, investigating the function and significance of autophagy in pathogenesis of OLP. Methods: Forty-one lesion tissues (OLP group, twenty-one cases of erosive OLP and twenty cases of non-erosive OLP) were selected from OLP patients visiting the Department of Periodontal and Oral Medicine, School and Hospital of Stomatology, Guizhou Medical University from October 2017 to December 2019. Fifteen cases of normal oral mucosal tissues (control group) were collected from oral and maxillofacial surgery at The Affiliated Stomatology Hospital of Guizhou Medical University during the same period. Protein and mRNA expression levels of LC3B, p62 and Beclin1 were detected by immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR) in OLP lesions respectively. The protein expression levels of LC3B, p62, Beclin1 and ratio of LC3B-Ⅱ/LC3B-Ⅰ in sixteen cases (eight cases of erosive OLP and eight cases of non-erosive OLP) from the OLP group were detected by Western blotting (WB). The potential relationship between LC3B, p62, Beclin1, LC3B-Ⅱ/LC3B-Ⅰ ratio and clinical features of OLP were analyzed. Results: IHC results showed that the positive expression rates of LC3B and p62 proteins in OLP lesion tissues [LC3B: 68% (28/41); p62: 59% (24/41)] were higher than those in the control group [LC3B: 5/15; p62: 3/15] (LC3B: χ²=5.55, P=0.019; p62: χ²=5.55, P=0.015). The positive expression rates of LC3B and p62 proteins in the erosive OLP group [LC3B: 86% (18/21); p62: 76% (16/21)] were higher than those in the non-erosive OLP group [LC3B: 50% (10/20); p62: 40% (8/20)] (LC3B: χ²=4.50, P=0.034; p62:χ²=5.53, P=0.019). The positive expression rate of Beclin1 protein in the OLP lesions[20% (8/41)] was lower than that in the control group (7/15) (χ²=4.13, P=0.042), but was not statistically different between the two types of OLP (P>0.05). The RT-qPCR results showed that the mRNA expression levels of LC3B and p62 in OLP lesions [LC3B: 2.78 (1.59, 6.15); p62: 4.30 (2.34, 6.29)] were higher than those in the control group [LC3B: 1.05 (0.88, 1.21); p62: 1.12 (0.89, 1.36)] (LC3B: Z=-4.56, P<0.001; p62: Z=-4.78, P<0.001), and the mRNA expression levels of LC3B and p62 in the erosive OLP group were higher than those in the non-erosive OLP group (LC3B: Z=-2.87, P=0.004; p62: Z=-2.95, P=0.003). The mRNA expression level of Beclin1 in OLP tissues was lower than that in the control group (Z=-2.43, P=0.015), but the difference was not statistically significant between the two types of OLP (P>0.05). WB results showed that the LC3B-Ⅱ/LC3B-Ⅰ ratio was higher in the OLP lesions than that in the control group (t=-2.45, P=0.021), and the LC3B-Ⅱ/LC3B-Ⅰ ratio was higher in the non-erosive OLP group than in the erosive OLP group (t=-2.38, P=0.032). Spearman's correlation analysis showed that the ratio was negatively correlated with the clinical staging and the degree of basal cell liquefaction in OLP (clinical staging: r=-0.57, P=0.021; basal cell liquefaction: r=-0.54, P=0.032), but not with the disease duration and the degree of lymphocytic infiltration (P>0.05). Conclusions: Autophagy related factors LC3B, p62 and Beclin1 may play a role in the formation and progression of OLP lesions. The autophagy level was relatively lack in erosive OLP compared to non-erosive OLP, contributing to the increased local lesion destruction in erosive OLP. Abnormal cellular autophagy may play an important role in the formation of OLP lesions.
Humans ; Lichen Planus, Oral/metabolism* ; Beclin-1 ; Microtubule-Associated Proteins/metabolism* ; Autophagy ; RNA, Messenger/metabolism*

OBJECTIVEThis study aimed to conduct a preliminary study on the possible role and significance of interleukin (IL)-12 and IL-27 in the pathogeneses of oral lichen planus (OLP).

METHODSThirty cases of patients with OLP (fifteen cases of reticular OLP and fifteen cases of erosive OLP) were enrolled in this study, and twenty cases of healthy people served as controls. Lymphocyte subsets CD3+, CD4+, CD8+, CD19+, and CD16+56 [natural killer cell (NK)] were tested using flow cytometry, and humoral immunity [immunoglobulin (Ig)G, IgA, IgM, C3, C4] were examined using nephelometry assays. IL-12 and IL-27 contents in serum of patients with OLP and normal controls were detected through enzyme linked immunosorbent assay. The correlations between the levels of IL-12, IL-27, immune status, and clinical characteristics of patients with OLP were analyzed, respectively.

RESULTSCD3+, CD4+, and CD8+in patients with OLP were markedly lower than the normal value, whereas CD 19+ of OLP in patients was significantly higher than the normal value (P<0.05). IgM inpatients with OLP was increased, whereas C4 was declined (P<0.05). IL-12 and IL-27 levels showed significant upregulation or ULF patients compared with control groups (P<0.05). Meanwhile, positive correlations existed between IL-12 andIL-27 levels in the serum of patients with OLP (r=0.912, P<0.01). No significant correlations of IL-12 and IL-27 epressions with clinical characteristics of OLP were found (P>0.05). Negative correlations of IL-12 and IL-27 levels with CD16+56(NK) cells were observed (r1 = -0.416, P1 = 0.022; r2 = -0.392, P2=0.032, respectively), whereas a positive correlation existed for IgG (r1=0.445, P1=0.014; n=0.549, P2=0.002, respectively).

CONCLUSIONA cellular immune dysfunction mainly dominate in patients with OLP, accompanied by some degree of humoral-immunity-function disorder. The abnormally high expressions of IL-12 and IL-27 are possibly synergized and promoted inflammation development in OLP. Its promotion takes place through the negatie feedback regulation of humoral immune responses, which are involved in the regulation of immune mechanisms of OLP.

Flow Cytometry ; Humans ; Immunoglobulins ; blood ; Interleukin-12 ; blood ; Interleukin-12 Subunit p35 ; metabolism ; Interleukin-27 ; blood ; Interleukins ; metabolism ; Killer Cells, Natural ; Lichen Planus, Oral ; blood ; immunology

In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.
Adult ; Aged ; Amphiregulin ; Betacellulin ; EGF Family of Proteins ; Epidermal Growth Factor ; metabolism ; Epiregulin ; Female ; Gene Expression Profiling ; Glycoproteins ; metabolism ; Heparin ; metabolism ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Keratinocytes ; metabolism ; Leukoplakia, Oral ; metabolism ; Lichen Planus, Oral ; metabolism ; Ligands ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Nerve Growth Factors ; Neuregulins ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Receptor, ErbB-4 ; Receptors, Cell Surface ; metabolism ; Transforming Growth Factor alpha ; metabolism ; Up-Regulation ; physiology

Antigen Presentation ; Apoptosis ; Hepatitis C ; Humans ; Lichen Planus, Oral ; etiology ; genetics ; pathology ; virology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic ; pathology ; T-Lymphocytes, Helper-Inducer ; pathology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo investigate the expressions of proliferating cell nuclear antigen (PCNA), B cell lymphoma-2 (Bcl-2) and Bcl-associated X (Bax) in the lymphocytes of patients with oral lichen planus (OLP).

METHODSImmunohistochemistry was used for detecting the expressions of PCNA, Bcl-2 and Bax proteins in oral lichen planus tissue and normal oral mucosa (NOM).

RESULTSThe expressions of PCNA and Bcl-2 proteins increased significantly in the lymphocytes of patients with OLP compared with those in NOM. The expressions of PCNA and Bcl-2 proteins showed no significant differences between patients with OLP of general type and erosive type.

CONCLUSIONIncreased expression of PCNA and the imbalance of Bcl-2/Bax expressions in the lymphocytes of patients with OLP can be important causes for continuous lymphocyte infiltration in OLP.

Adult ; Female ; Humans ; Lichen Planus, Oral ; metabolism ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-X Protein ; metabolism

OBJECTIVETo investigate the expression of TGF-beta receptors in CD8+ T cells of oral lichen planus (OLP).

METHODSImmunohistochemical double labeling technique was used to examine the expression of TGF-betaR I and TGF-betaR II in CD8+ T cells of 28 OLP patients and in 10 controls. The results were compared between the two groups.

RESULTSThe double labeled cells were negative in controls. The positive rates of double labeled cells of CD8+/TGF-betaR I and CD8+/TGF-betaR II in OLP were (8.82 +/- 9.98)% and (1.11 +/- 2.94)% respectively.

CONCLUSIONSThe expression level of TGF-betaR II in CD8+ T cells of OLP did not increase compared with the controls, but the expression of TGF-betaR I increased. The results indicate the abnormal TGF-beta signal transduction in CD8+ T cells of OLP, which may contribute to the persistence of the chronic inflammation in OLP.

Adult ; CD8-Positive T-Lymphocytes ; metabolism ; Case-Control Studies ; Female ; Humans ; Lichen Planus, Oral ; metabolism ; pathology ; Male ; Mouth Mucosa ; metabolism ; pathology ; Protein-Serine-Threonine Kinases ; metabolism ; Receptors, Transforming Growth Factor beta ; metabolism ; Signal Transduction

OBJECTIVETo examine the expression of TGF-beta1, Smad7 and cell apoptosis in oral lichen planus (OLP) and to evaluate the possible pathogenesis of oral lichen planus.

METHODSImmunohistochemical technique was used to study the expression of TGF-beta1 and Smad7 in the epithelia cells of 17 OLP cases and 7 normal oral mucosa (NOM). TUNEL was used for detecting the cell apoptosis in 17 OLP cases and 7 NOM.

RESULTSTGF-beta1 was moderately positive in the epithelia cells of OLP. All the epithelia cells in OLP showed strong cytoplasmic staining. The expression of TGF-beta1 and Smad7 were significantly increased in OLP compared with that in NOM (P < 0.05). Cell apoptotic index (AI) was remarkably increased in epithelia cells in OLP cases, and the cell apoptosis was localized in basal and suprabasal epithelial layers. There was a positive correlation between TGF-beta1 expression and cell apoptosis in the epithelia of OLP (r = 0.69, P <0.05).

CONCLUSIONSHigh expression of TGF-beta1 and Smad7 in the epithelia of OLP suggests that TGF-beta1-Smad7 signal pathway was disturbed in oral lichen planus. The imbalance of TGF-beta1-Smad7 pathway may contribute to the mechanisms of cell apoptosis of epithelial cells in OLP.

Apoptosis ; Case-Control Studies ; Epithelium ; metabolism ; pathology ; Female ; Humans ; Lichen Planus, Oral ; metabolism ; Male ; Mouth Mucosa ; metabolism ; pathology ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo examine the expression and distribution of NF-kappaBp65, TRAF2, and cyclinD1 and their association with cell apoptosis in oral lichen planus (OLP).

METHODSSixty OLP patients were divided into erosion-atrophy group (n=30) and non-erosion group (n=30) according to their clinical features. Immunohistochemistry with SP method was used to detect the expressions of NF-kappaBp65, TRAF2, cyclinD1 in the 60 OLP and 40 normal oral mucosa (control) specimens. TUNEL assay of randomly selected specimens from 10 normal and 15 OLP cases was performed to detect the cell apoptotic index (AI).

RESULTSCompared with the control group, OLP group showed significantly increased AI of the epithelial cells (67.32-/+18.99) and decreased AI of the lymphocytes (34.12-/+9.89) (P<0.05). In the OLP group, the positivity rates for NF-kappaBp65, TRAF2, and cyclin D1 in the epithelial cells (85.00%, 76.67% and 71.67%, respectively) and in the lymphocytes (91.67%, 86.67% and 70.00%, respectively) were all significantly higher than those in the control group (P<0.05). NF-kappaBp65 expression was significantly increased in the lamina propria in the non-erosion OLP group as compared to the erosion-atrophy group. A positive correlation was noted between lymphocyte NF-kappaBp65 expression and AI of the epithelial cells, but an inverse correlation found between lymphocyte NF-kappaBp65 expression and the AI of the lymphocytes. Lymphocyte TRAF2 and cyclin D1expressions were also inversely correlated to lymphocyte AI. There was a positive correlation between TRAF2 and cyclin D1 expressions and the expression NF-kappaBp65 in the epithelial cells and lymphocytes in OLP.

CONCLUSIONSAccelerated apoptosis of the keratinocytes and inhibition of lymphocyte apoptosis may coexist to contribute to the formation and progression of OLP. NF-kappaBp65 expression, particularly its abnormal nuclear expression, may play a partial role in the pathogenesis of OLP.

Adult ; Aged ; Apoptosis ; Cyclin D1 ; metabolism ; Epithelial Cells ; metabolism ; Female ; Humans ; Lichen Planus, Oral ; metabolism ; Lymphocytes ; metabolism ; Male ; Middle Aged ; TNF Receptor-Associated Factor 2 ; metabolism ; Transcription Factor RelA ; metabolism ; Young Adult

OBJECTIVETo investigate the role of MMP-2, MT1-MMP and TIMP-2 in the carcinogenesis of oral lichen planus (OLP).

METHODSImmunohistochemistry was performed to examine the expression of OLP and compare with that of NOM.

RESULTSThe expression of these proteinases significantly increased from NOM, non-atrophic OLP, to atrophic OLP and OSCC. The expression of MMP-2 and MT1-MMP in atrophic OLP was significantly higher than in non-atrophic OLP. Furthermore, the expression of TIMP-2 consequently increased with the increasing of the MMP, but the increase of TIMP-2 was less than that of MMP.

CONCLUSIONSMMP may be useful marker to judge the possibility of malignant change of OLP.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Lichen Planus, Oral ; metabolism ; pathology ; Matrix Metalloproteinase 14 ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; Mouth Mucosa ; metabolism ; pathology ; Mouth Neoplasms ; metabolism ; pathology ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism

OBJECTIVETo explore the expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), c-fos and c-jun in oral lichen planus (OLP).

METHODSThe levels of gene expression of EGF, EGFR, c-fos and c-jun were detected with reverse transcription-polymerase chain reaction (RT-PCR) in 10 cases of erosive OLP, 12 cases of reticular OLP and 9 cases of normal oral mucosa. Protein contents and distribution of EGF, EGFR, C-fos and C-jun were examined with immunohistochemical technique in different tissues.

RESULTSThe endogenous levels of EGFR mRNA and protein in erosive OLP were (55.9 +/- 23.1)% and (71.1 +/- 10.1)%, respectively, and significantly higher than those in reticular OLP and normal oral mucosa. The mRNA contents of c-fos and c-jun were significantly higher in erosive OLP than in normal oral mucosa. The positive cell rates of c-fos and c-jun protein in erosive OLP were 1.3 and 1.5 times of those in normal oral mucosa, respectively (P < 0.05).

CONCLUSIONSThe probability of carcinomatous change of erosive OLP might be higher than that of reticular OLP, in which EGF and EGFR might play an important role.

Adult ; Case-Control Studies ; Epidermal Growth Factor ; metabolism ; Humans ; Lichen Planus, Oral ; metabolism ; pathology ; Middle Aged ; Mouth Mucosa ; metabolism ; pathology ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; RNA, Messenger ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism