| Summary: | 碩士 === 國立陽明大學 === 口腔生物研究所 === 99 === Areca quid chewing (AQ) is popular in Taiwan, India, and many southeast-Asian countries. Areca quid chewing is associated with several oral diseases, including oral cancer and periodontitis. Periodontitis is an inflammatory disease with tissue destruction and alveolar bone loss. Inflammatory reaction may promote the differentiation of osteoclasts and the progression of diseases. Peripheral blood mononuclear cells (PBMC) play an important role in the regulation of inflammatory and immune systems. This study was to determine the effects of areca nut extract (ANE) on the human immune cells—PBMC. Aim (1) was to investigate the influence of ANE on the expression of inflammatory bone-resorbing mediators. Aim (2) was to define the profile of global inflammatory gene expression in ANE-treated PBMC and involved mechanisms. The results showed that ANE enhanced the production of osteoclastogenic molecules, monocyte chemoattractant protein-1 (MCP-1) and granulocyte-macrophage colony-stimulating factor (GMCSF), and the cellular expression of receptor activator for nuclear factor kappa B ligand (RANKL). The up-regulated and down-regulated genes (transcripts) extracted from microarray data of ANE-stimulated PBMC were further analyzed by Gene Ontology term, inflammatory response. The results found that 18 inflammatory genes were shown to be up-regulated while 6 inflammatory genes were down-regulated. A protein-protein interaction (PPI) network was able to be constructed by the up-regulated inflammatory genes. The up-regulation of selected inflammatory genes (MCP-1, CCL7, CCL8, CCR1, CCR3, CCR5, STAT1, GMCSF, TNF and IFN-G) was confirmed by the quantitative real-time reverse transcription-polymerase chain reaction (Q-RT-PCR). Up-regulation of these inflammatory genes was inhibited by antioxidants including curcumin, PDT or DPI, and inhibitors of nuclear factor-kappa?羠 (NF-kappa B), JAK-STAT or phosphoinositide 3-kinase (PI3K). Data suggested that ANE stimulated expression of inflammatory genes in PMBC was related to the production of ROS, and the activation of NF-kappa?羠, JAK-STAT and PI3K signaling pathways. The results will contribute to the understanding of the effects of areca quid chewing on immune functions, and thus, the prevention of the related oral diseases.
|
|---|
