ABSTRACT
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.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Amphiregulin , Betacellulin , EGF Family of Proteins , Epidermal Growth Factor , Metabolism , Epiregulin , Gene Expression Profiling , Glycoproteins , Metabolism , Heparin , Metabolism , Heparin-binding EGF-like Growth Factor , Intercellular Signaling Peptides and Proteins , Metabolism , Keratinocytes , Metabolism , Leukoplakia, Oral , Metabolism , Lichen Planus, Oral , Metabolism , Ligands , Mouth Mucosa , Metabolism , Nerve Growth Factors , Neuregulins , Metabolism , RNA, Messenger , Metabolism , Real-Time Polymerase Chain Reaction , ErbB Receptors , Metabolism , Receptor, ErbB-2 , Metabolism , Receptor, ErbB-3 , Metabolism , Receptor, ErbB-4 , Receptors, Cell Surface , Metabolism , Transforming Growth Factor alpha , Metabolism , Up-Regulation , PhysiologyABSTRACT
Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8– and CD8+CD4– T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection. The epitopes recognized by DENV-specific T cells are located in most of the structural and non-structural proteins, but NS3 is the protein that is most dominantly recognized. In patients with dengue hemorrhagic fever (DHF) caused by secondary DENV infection, T cells are highly activated in vivo. These highly activated T cells are DENV-specific and oligoclonal. Multiple kinds of lymphokines are produced by the activated T cells, and it has been hypothesized that these lymphokines are responsible for induction of plasma leakage, one of the most characteristic features of DHF. Thus, T-cells play important roles in the pathogenesis of DHF and in the recovery from DENV infection.