Genome-wide analysis reveals the active roles of keratinocytes in oral mucosal adaptive immune response

Abstract

To elucidate the roles of oral keratinocytes in the adaptive immune response of oral mucosa, global gene expression analysis was performed by microarray technique and integrating computational methods, including hierarchical clustering, biological process Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, self-organizing maps (SOMs) and biological association network analysis (BAN). Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database, http://www.ncbi.nlm.nih.gov/geo/ (GEO accession GSE28035). We identified 666 differentially expressed genes in the early stage (48 h) and 993 in the late stage (96 h) of the oral mucosal adaptive immune response. The analysis revealed that oral keratinocytes exerted diverse biological functions in different stages of immune response. Specifically, in 48 h the differentially expressed genes encompassed an array of biological ontology associated with immune response, such as antigen processing and presentation, and positive regulation of T-cell-mediated cytotoxicity. Several pathways which have been reported to be critical in inflammation, including mitogen-activated protein kinase pathway, were activated. Furthermore, after BAN construction, some putative hub genes and networks such as interleukin-1α and its subnetwork were recognized. Taken together, these results give substantial evidence to support the active roles of keratinocytes in the oral mucosal adaptive immune response.

Modulation of IL-1β reprogrammes the tumor microenvironment to interrupt oral carcinogenesis

“…The details of the protein isolation and western blot analysis have been described in a previous study 31 . A specific anti-human IL-1β antibody (1:1000), an anti-human β-actin antibody (1:1000) from Cell Signaling Technology (Danvers, MA, USA) and horseradish peroxidase conjugated goat secondary antibodies (Beyotime Institute of Biotechnology, Haimen, Jiangshu China) were used in this study.…”

“…The microarray data were processed and analyzed as described previously 31 . A differentially expressed gene was defined as a variation in gene expression no less than 2-fold or 1.5-fold with a detection P value of less than 0.05.…”

“…This software package generates interaction networks, starting with a differentially expressed gene list, by the information present in a database of known molecular interactions. Details of this network construction have been described in a previous study 31 .…”

Thymic stromal lymphopoietin: Next research hotspot of carcinogenesis?

“…However, many details underlying effect of TSLP on cacinogenesis such as signal transduction mechanisms are largely unknown. Our previous study found that TSLP was expressed on mouse oral keratinocyte under inflammation [29], and TSLP and its receptor were detected on oral squamous cell carcinoma cell line (unpublished data). Whether TSLP is also involved in the carcinogenesis in other epithelial tumor type which progression have been reported to be associated with immune disregulation and elevated Th2 cytokines expression such as head and neck carcinoma remains to be fully elucidated in further study [30,31].…”

Development of Oral Epithelial Cell Line ROE2 with Differentiation Potential from Transgenic Rats Harboring Temperature-Sensitive Simian Virus40 Large T-Antigen Gene

“…Very interestingly, the top biological function in both upregulated gene clusters Up-II and Up-III was the biological process of skin development. Among a total of 32 genes identified (9 + 23; Table 1), 28 genes (the exceptions being Prdm1 , Calml5 (calmodulin-like 5), Foxe1 (forkhead box E1), and Tfap2a (transcription factor AP-2 alpha)) were also found to be expressed in normal differentiated keratinocytes in mouse oral mucosa [53], the gene expression data of which were obtained from GEO, an accession number of GSE28035. In these genes, it has been reported that Evpl (envoplakin) [35], Scel (sciellin) [4], Tgm1 [8], and Tgm3 [56] are involved in the development of epidermis.…”