Rui Lu

Wuhan University, Wu-han-shih, Hubei, China

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Publications (14)25.69 Total impact

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    ABSTRACT: Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling pathway and has been implicated in the pathogenesis of many chronic inflammatory and immune disorders. Here we investigated whether the IL-23/IL-17 axis was present and functional in the lesions of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. Using immunohistochemistry and quantitative PCR, we found that the subunits of IL-23 and IL-17 were overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues. Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients. Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes. Taken together, our results revealed an overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the complex immune network of OLP lesions.
    Mediators of Inflammation 07/2014; 2014:701094. DOI:10.1155/2014/701094 · 2.42 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Oral potentially malignant disorders (OPMDs) are chronic inflammatory diseases in which cells suffer hypoxia referring to deprivation of adequate oxygen supply. Hyperbaric oxygen treatment (HBO), which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve or cure disorders involving hypoxia. Although the applications of HBO in wound healings, acute ischemic stroke, radiation-induced soft tissue injury and cancers are extensively reported, there are only few studies on their effect in OPMDs. Not only does HBO furnish oxygen-it also possesses potent anti-inflammatory properties. At the cellular level, HBO can decrease lymphocyte proliferation and promote apoptosis of fibroblasts. At the molecular level, it can decrease expression of HIF, ICAM-1, TNF-α, TGF-β, and IFN-γ, as well as increase vascular VEGF expression and angiogenesis. Thus, we hypothesize that HBO may contribute to treat OPMDs, including oral lichen planus, oral leukoplakia, and oral submucous fibrosis both at the cellular level and the molecular level, and that it would be a safe and inexpensive therapeutic strategy.
    Medical Hypotheses 05/2014; DOI:10.1016/j.mehy.2014.05.011 · 1.15 Impact Factor
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    ABSTRACT: 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.
    Journal of Oral Pathology and Medicine 12/2013; 44(1). DOI:10.1111/jop.12142 · 1.87 Impact Factor
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    ABSTRACT: Objective : Follicular helper T cells, a novel Th-cell subset providing a helper function to B cells, has been recently shown to play a role in T cell–mediated organ-specific autoimmunity. The present study aimed to assess the proportions of Tfh cells in peripheral blood mononuclear cells (PBMCs) from patients with oral lichen planus (OLP), and their correlations with the disease severity. Methods : Twenty-three OLP patients, including 10 with erosive form and 13 with reticular form, and 10 healthy controls were recruited. The disease severity was assessed by RAE (reticular, atrophic, erosive lesion) scoring system. The proportions of Tfh cells and B cells in PBMCs were detected by Flow cytometry. Results: When the OLP patients were regarded as a whole group, there was no significant difference of Tfh cell and B cell proportions in PBMCs between OLP patients and healthy controls. However, the proportions of Tfh cells in both PBMCs and peripheral CD4+T cells from erosive-OLP patients were significantly higher than reticular-OLP patients and healthy controls, without alteration of proportions of peripheral B cells. In addition, The frequencies of Tfh cells in PBMCs from OLP patients were positive correlated with the RAE scores. Conclusion : Our results suggested increased proportions of Tfh cells in PBMCs from patients with erosive-OLP, which may be involved in the autoimmune pathogenesis of the disease. Moreover, the frequency of Tfh cells in PBMCs may be useful to evaluate the severity of OLP patients.
    IADR Asia/Pacific Region (APR) Regional Meeting and Co-Annual Scientific Meeting of IADR Divisions 2013; 08/2013
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    ABSTRACT: Objectives: The stem cell-associated protein HIWI is a human homologue of the piwi family, which play an improtant role in stem cell self-renewal and division. Aberrant expression of Hiwi has been found in various malignant tumors and to be associated with the poor prognosis. The aim of the present study was to examine the expression pattern of HIWI in the oral cancer and precancerous lesions. Methods: Expression of HIWI was analysis by Immunohistochemical in specimens from 20 cases of oral squamous cell carcinoma (OSCC), 51 cases of oral epithelial dysplasia (OED), 17 cases of oral epithelial hyperplasia (OEH) and 16 cases of normal oral epithelium (NOE). The positive rates of HIWI expression in each group were calculated and compared. Results: Positive expressions of HIWI was observed in 9 (55%) cases of OSCC, 41 (80.4%) cases of OED, 14 (82.3%) cases of OEH and 15 (93.8%) cases of NOE, respectively. The positive rate of HWI in the OSCC group was significantly decreased than that in the OED (P<0.05) and the NOE (P<0.05) groups, but not in the OEH group (P>0.05). Conclusions: The expression of HIWI in OSCC was down-regulated compared with the normal oral epithelium and oral epithelial dysplasia, suggesting its possible involvement in the processes of malignant transformation of oral epithelium.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
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    ABSTRACT: 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.
    Cytokine 03/2013; 62(1). DOI:10.1016/j.cyto.2013.01.020 · 2.87 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the anticancer property of vesicular stomatitis virus matrix protein (VSVMP) in oral squamous cell carcinoma (OSCC) via in vitro and in vivo approaches. In this study, we found that OSCC cells treated with VSVMP showed retarded cell growth in vitro. The percentage of apoptotic cells in VSVMP group was much higher than that of the control groups. Moreover, our in vivo experiments showed that the growth of tumor xenografts was significantly suppressed by VSVMP treatment without any obvious side effects. Further studies revealed that the suppression of tumor growth may be caused by the synergistic effect of VSVMP related cell apoptosis enhancing and tumor angiogenesis suppression, and the latter is most likely correlated with the suppression of VEGF pathway. This study indicated that VSVMP treatment can effectively inhibited the cell growth and tumor angiogenesis in OSCC without obvious adverse effects. Therefore, VSVMP might be a potential and efficient strategy for OSCC treatment.
    Oral Oncology 02/2012; 48(2):110-6. DOI:10.1016/j.oraloncology.2011.09.007 · 3.03 Impact Factor
  • Journal of the American Academy of Dermatology 09/2011; 65(3):677-9. DOI:10.1016/j.jaad.2010.07.007 · 5.00 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the potential pro-inflammatory role of the cytokine interleukin (IL-18) in oral lichen planus (OLP) so as to provide a reliable and early indicator for the diagnosis of OLP. One hundred three ethnic Chinese patients with OLP were enrolled in this study, as were 48 age- and sex-matched controls. IL-18 concentrations in serum and saliva were screened by enzyme-linked immunosorbent assay. The protein content was expressed as picograms per milliliter. OLP patients showed a high-level of IL-18 expression profile in serum compared with the control group (OLP = 21.32 ± 8.26 pg/mL, control = 12.29 ± 5.11 pg/mL, P < 0.05), and the saliva partner had significantly higher concentrations of IL-18 compared to the control (OLP = 20.12 ± 5.78 pg/mL, control = 15.60 ± 4.17 pg/mL, P < 0.05). In patients with OLP, serum and salivary IL-18 are elevated, correlating with the severity of illness. These findings may be considered to improve the predictive or prognostic values of inflammatory cytokines for OLP and also to design possible novel therapeutic approaches.
    Inflammation 04/2011; 35(2):399-404. DOI:10.1007/s10753-011-9327-3 · 1.92 Impact Factor
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    ABSTRACT: Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells is unknown. We investigated the antitumor activities of HNK on OSCC cells in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 microg x mL(-1) or 20 microg x mL(-1) of HNK were more stronger compared with those of 20 microg x mL(-1) 5-fluorouracil (5-Fu, the control) applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.
    International Journal of Oral Science 01/2011; 3(1):34-42. DOI:10.4248/IJOS11014 · 2.03 Impact Factor
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    ABSTRACT: 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.
    Journal of Oral Pathology and Medicine 12/2010; 40(5):361-8. DOI:10.1111/j.1600-0714.2010.00991.x · 1.87 Impact Factor
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    ABSTRACT: Oral 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. Expressions 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. When 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. The 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.
    Archives of oral biology 12/2010; 56(5):499-505. DOI:10.1016/j.archoralbio.2010.11.006 · 1.65 Impact Factor
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    ABSTRACT: Nuclear 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. Thirty 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. Nuclear 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. Nuclear 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.
    Journal of Oral Pathology and Medicine 06/2009; 38(7):559-64. DOI:10.1111/j.1600-0714.2009.00779.x · 1.87 Impact Factor
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    ABSTRACT: Objective: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory oral mucosal disorder of unknown etiology. Imbalance of the cytokines produced by two subsets of T-helper cells, Th1 and Th2, probably contributes the pathogenesis of OLP. Growing evidences have 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 present study was designed to compare the mRNA expressions of T-bet and GATA-3, as well as their ratio, in peripheral blood mononuclear cell (PBMC) from OLP patients versus health controls. Methods: PBMC were isolated from reticular and erosive OLP patients and healthy individuals by density gradient centrifugation. Expressions of T-bet and GATA-3 mRNA in the PBMCs were detected by the real-time quantitative polymerase chain reaction. Results: When all OLP patients were regarded as a whole group, T-bet mRNA level was significantly increased (P<0.01) while no statistical difference in GATA-3 mRNA level was found in OLP patients, compared with heathy controls. In addition, the ratio of T-bet/GATA-3 mRNA expression in OLP patients was significantly higher (P<0.05). When the patients were divided into erosive group and reticular group, however, only T-bet mRNA level (P<0.01) and the ratio of T-bet/GATA-3 mRNA expression from reticular OLP patients were significantly higher than those in control group (P<0.05). Neither T-bet nor GATA-3 mRNA level, nor the ratio of T-bet/GATA-3 mRNA expression in PBMC from erosive OLP patients showed statistical difference.Conclusion: Patients with OLP have increased level of T-bet mRNA and the higher T-bet/GATA-3 mRNA ratio, indicating a predominant role of Th1-type immune response in pathogenesis of OLP. Different gene expression patterns of T-bet and GATA-3 may indicate different immunoregulatory mechanisms in different forms of OLP. Key words: Oral lichen planus; Th1; Th2; T-bet; GATA-3
    2nd Meeting of IADR Pan Asian Pacific Federation (PAPF) and the 1st Meeting of IADR Asia/Pacific Region 2009;