趨化激素及其受體在台灣異位性皮膚炎疾病中之角色探討

Roles of chemokines and chemokine receptors among patients with atopic dermatitis in Taiwan

黃逸明(Yi-Ming Huang)

指導教授 ： 李婉若

臺北醫學大學/醫學院/醫學科學研究所/碩士(2003年)

摘要

異位性皮膚炎是一種慢性反覆的發炎性皮膚疾病，病患通常搔癢難耐，並且在特定部位有濕疹樣變化，患者個人或家族常有異位性體質(Atopy)。CC趨化激素是具有促發炎能力的分子，在異位性皮膚炎與過敏的病理機轉扮演重要角色。我們利用ELISA來檢測病人組與對照組血漿中趨化激素的濃度，並使用流式細胞儀來測量週邊血液單核球上趨化激素受體的表現量。實驗結果顯示病人組血漿中的免疫球蛋白E、RANTES、MIP-1與Eotaxin的濃度較對照組高。病人組血漿中的MCP-1較對照組低。趨化激素受器CCR2、CCR3與CCR5在兩組間表現並無差異。此外，RANTES啟動子區域的多型性對於RANTES的分泌量與異位性皮膚炎盛行率的影響已被廣泛討論，之前的研究顯示在德國與匈牙利異位性皮膚炎病童中RNATES啟動子的多型性與疾病有不同的相關性，因此我們利用聚合脢連鎖反應與直接定序法來分析台灣地區異位性皮膚炎患者與對照組的RANTES啟動子區域的多型性。結果顯示，兩者之間的多型性表現並無差異。綜合以上研究，IgE與CC趨化激素中的RANTES、MIP-1、Eotaxin在台灣地區異位性皮膚炎患者體內的表現量確實有上升，而RANTES驅動子在-28與-403位置產生的多型性與異位性皮膚炎並無相關。

關鍵字

趨化激素 ； 異味性皮膚炎 ； 基因多型性

並列摘要

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by extreme pruritus, typically distributed eczematous skin lesions and a personal or family history of atopic diseases. CC chemokines are potent proinflammatory molecules which play an important role in the pathophysiology of atopic dermatitis (AD) and allergy. We determined the plasma level of C-C chemokines of AD and controls by ELISA and used flow cytometry to evaluate expression of chemokine receptors on peripheral blood mononuclear cells in both groups. Plasma levels of IgE, RANTES, MIP-1, and eotaxin were increased in severe AD patients, but not in moderate and mild AD compared with normal controls. MCP-1 level is lower in the patient group. Chemokine receptor CCR2, CCR3 and CCR5 were the same in both AD and control group. In addition, polymorphisms in promoter region of RANTES have been found, which increase the expression of these chemokines and affect the prevalence of atopic dermatitis. Different studies showed various roles of RANTES polymorphism in atopic dermatitis of German and Hungarian children. We also investigated whether the presence of these polymorphisms was associated with atopic dermatitis in Taiwan. Atopic dermatitis patients and controls were screened for genotype with a PCR and direct sequencing- based assay. No significant difference in the frequency of the polymorphisms between atopic dermatitis patients and controls was found. Our finding suggests augmented production of some CC-chemokine such as RANTES, MIP-1, and eotaxin but no MCP-1 correlates with clinical severity of atopic dermatitis. In Taiwan population, there was no association between the -28G and -403A alleles polymorphism in the RANTES promoter and atopic dermatitis.

並列關鍵字

chemokine ； atopic dermatitis ； gene polymorphism

參考文獻

Valente AJ, Graves DT, Vialle-Valentin Ce, et al. Purification of a monocyte chemotatic factor secreted by nonhuman primate vascular cells in culture. Biochemistry 27:4162, 1988. Wu CS. Yu CL. Chang CH. Kuo WR. Lin HJ. Yu HS. Effect and correlation of serum total IgE, eosinophil granule cationic proteins and sensitized allergens in atopic dermatitis patients with or without rhinitis. Kaohsiung J Med Sci 18:229-35, 2002.

Al Sharif F, Ollier WE, Hajeer AH. A rare polymorphism at position -28 in the human RANTES promoter. Eur J Immunogenet 26:373-374,1999.

Andrew DL. The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol 14:129-135, 2002 Anonymous.

Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 186:23-31,1993.

Azzawi M, Pravica V, Hasleton Ps, et al. A single nucleotide polymorphism at position -109 of the RANTES proximal promoter. Eur J Immunogenet 28:95-96,2001.