Abstract
摘要:嚼食檳榔(Areca quid)在印度及東南亞地區是一個相當常見的習慣,流行病學的研究顯示嚼食檳榔和罹患口腔鱗狀上皮細胞癌(oral squamous cell carcinoma)以及口腔黏膜下纖維化(oral submucous fibrosis)等疾病密切相關。根據統計,台灣嚼食檳榔的人口超過200萬,而口腔鱗狀上皮細胞癌更是高居男性癌症患者死亡率的第五位。實驗證據顯示鱗狀上皮細胞癌的病變原因和病人免疫機能的惡化有密切關聯性,免疫系統是體內對抗腫瘤形成的重要防禦機制,免疫細胞所表現的細胞激素(cytokine)對腫瘤生長有很大的影響,細胞激素在體內對抗惡性腫瘤細胞的免疫機能上扮演非常顯著的角色。研究報告指出口腔癌和口腔黏膜下纖維化病人,與正常的對照組比較,其T細胞和B細胞免疫反應明顯變差,且在口腔病變組織中有較多的免疫細胞浸潤(infiltration),進一步分析發現在口腔病變組織中的免疫細胞主要是T細胞,其中大部分細胞處於活化狀態且CD4+細胞/CD8+細胞的比值明顯升高。上述研究結果指出T細胞免疫反應的改變在口腔癌以及口腔黏膜下纖維化的病變過程中可能扮演著重要的角色。然而,
Abstract: Epidemiological studies have revealed that areca quid (AQ) chewing, a popular habit in India and Southeast Asia, is associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). In Taiwan, more than 2 million people have the habit of AQ chewing and OSCC is the 5th leading cause of male cancer mortality. Experimental evidence suggests that the pathogenesis of squamous cell carcinoma is associated with deterioration in the immunological status. The host immune system is an important defense mechanism against tumor formation. The cytokine network of the immune system possesses profound effects on the growth of tumors in vivo and plays a significant role in the immunosurveillance against malignant cells. Deficiencies in both T and B cell-mediated immune responses have been reported in patients with oral cancers or OSF. Histological studies showed an increased infiltration of immune cells in oral tissue specimens from patients with oral carcinoma or OSF. The major immunocompetent cells found in the lesions of both oral cancer and OSF patients were T lymphocytes with an increased CD4+ to CD8+ ratio. Furthermore, both CD4+ and CD8+ lymphocytes were in an activated state (HLA-DR+) in the peripheral blood and tumor tissue of oral cancer patients. Together these findings indicate that altered T cell-mediated cellular immune responses may play a role in the pathophysiology of oral cancer and OSF. However, to date little is known with respect to the immunotoxicology of AQ. The influence of AQ ingredients on T cell activation and cytokine gene expression has not been critically and systemically addressed. Thus, the objective of the proposed research project is to study the effect of AQ ingredients on T-cell gene expression and to investigate the possible underlying mechanism. The results from this project will provide further insights into our understanding to the potential impact of AQ on the immune system. The specific aims (SA) of this initial project are as follows:
1. Characterize the influence of AQ ingredients, such as arecoline and safrole (a major ingredient of Piper betle inflorescence that is a component of AQ), and total areca nut extracts on the profile of cytokine gene expression by murine splenic T cells. The cells will be stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. RNase protection assays (RPA) will be employed to simultaneously examine the steady state mRNA expression of multiple cytokines, including IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-15 and IFN-.
2. Further investigate the effect of AQ ingredients on T cell activation, as assessed by IL-2 expression. In addition to utilize RPA stated in SA1, IL-2 mRNA expression will be further measured by quantitative RT-PCR. IL-2 protein secretion will be determined by ELISA.
3. Investigate the potential underlying mechanism by which AQ ingredients modulate the expression of T cell cytokines, including IL-2 and other cyt
Keyword(s)
檳榔
免疫
T細胞
細胞激素
基因表現
areca quid
immune
T cell
cytokine
gene expression